Engineered parasites for delivering protein to the central nervous system (CNS)

ABSTRACT

Provided are nucleic acid constructs, Toxoplasma comprising same, pharmaceutical compositions comprising same and methods using same for delivering a protein-of-interest to a tissue-of-interest of a subject, such as the CNS and further treating a pathology which is treatable by administration of a therapeutic polypeptide in a central nervous system of the subject.

RELATED APPLICATIONS

This application is a National Phase of PCT Patent Application No. PCT/IL2017/050731 having International filing date of Jun. 29, 2017, which claims the benefit of priority under 35 USC § 119(e) of U.S. Provisional Patent Application No. 62/355,898 filed on Jun. 29, 2016. The contents of the above applications are all incorporated by reference as if fully set forth herein in their entirety.

SEQUENCE LISTING STATEMENT

The ASCII file, entitled 74636SequenceListing.txt, created on Dec. 24, 2018, comprising 17,070,469 bytes, submitted concurrently with the filing of this application is incorporated herein by reference. The sequence listing submitted herewith is identical to the sequence listing forming part of the international application.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to a nucleic acid construct for the secretion of a pharmaceutical polypeptide fused to a Toxoplasma gondii secreted polypeptide, and Toxoplasma comprising same, and, more particularly, but not exclusively, to a pharmaceutical compositions and methods of using same for treating a subject.

The lack of robust methods for the delivery of protein therapeutics is to a great degree the current bottleneck in their translation into clinical treatment. Proteins often serve a highly specific and complex set of functions that cannot be mimicked by simple chemical compounds (Nat Rev Drug Discov. 2008; 7(1):21-39. Protein therapeutics: a summary and pharmacological classification. Leader B, Baca Q J, and Golan D E); however, owing to their macromolecular nature, the delivery of therapeutic protein to target sites in the body is extremely challenging. Low functional stability and rapid loss of activity following administration or during storage, along with low permeability through biological barriers, limit the delivery of active proteins. The ongoing development of chemical modifications, conjugates and carrier systems aided the delivery of some therapeutic proteins, but these are mostly still limited to targets within the “accessible target space”—in the vascular compartment or on the surface of cells (Mitragotri 2014, Nat. Rev. Drug. Discov. 13(9):655-72). Efficient delivery is particularly challenging in the field of neurological diseases due to the blood-brain barrier (BBB), which tightly regulates the transport of molecules to the brain, while further complexity is added when the target is intracellular.

In order to deliver supplementary proteins to cells within the CNS, it is necessary to develop mechanisms that penetrate the BBB and may target specific cells within the CNS.

Currently, the major approaches for treating conditions caused by a deficiency of a specific protein are gene therapy, stem cell therapy and enzyme replacement therapy.

Gene therapy is the insertion of a functional copy of a gene that encodes a therapeutic protein (Cox, D. B. T., et al., 2015) which aims to increase the expression of a functional copy of the protein. While gene therapy provides the correct sequence of the gene, it does not address loss of protein function that is caused by or accompanied by defects in translational mechanisms or post-translational modifications. In addition, it can bear the risk of cancer development due to insertional mutagenesis (Persons, D. A. & Baum, C. 2011), mobilization, germline transmission, immunogenicity and limited transgene capacity (Schambach, A., et al., 2013; Al-Dosari et al., 2009). To target the CNS, gene therapy is most commonly mediated by the use of viral vectors, including those derived from herpes simplex virus type 1 (HSV-1), adenovirus, AAV, lentiviruses such as HIV-1, feline immunodeficiency virus or equine infectious anemia virus, and more recently SV40-AAV and lentivirus which are currently the most common of those. While some viral vectors are safer than the others, they do not address protein processing defects, and clinical efficiency remains limited.

Stem cell therapy relies on the protein synthesis mechanisms of implanted cells which can supplement the defective endogenous synthesis of the protein. Despite numerous efforts to implement this approach clinically, the efficiency of such treatments is reduced by rejection of implanted cells, and the low cost-efficiency of using patient-specific stem cells. In addition, the risks involved in stem cell treatments include complications associated with immunosuppression required to reduce rejection of grafted cells, and the development of cancer (Dimmeler, S., et al., 2014).

Protein- or Enzyme replacement therapy (ERT), in which the supplementary protein is synthesized externally and then delivered into the CNS, must overcome the impermeability of the BBB, and develop precise targeting in order to be clinically relevant. One such approach to protein delivery is injection directly into the brain or into adjacent organs from which the protein may diffuse at a low efficiency. Thus, in addition to the risk of such approaches, the ability to target specific regions within the CNS with the necessary amount is limited. Another problem of such approaches is the requirement of repeated dosing, which is often clinically impractical (Abbott, N.J. 2013).

ERT can be combined with an increase in BBB permeability to allow the therapeutic protein to diffuse into the CNS with greater efficiency (Malhotra, M. & Prakash, S. 2011). This is achieved through the shrinking of the cells that compose the BBB, or manipulation of the transport mechanisms through the BBB. However, this approach is not efficient due to opsonization, and bears the risk of unwanted substances diffusing into the CNS along with the supplemented protein of interest (Bradbury, M. W. B. 2012).

An alternative approach is the attachment of the therapeutic protein to elements that enter the CNS to utilize their inherent ability to cross the BBB. Agents that may mediate trafficking across the BBB include fusion proteins, dendrimers, solid lipid nanoparticles, liposomes and nanoparticles (Solaro, R., 2010). However, these approaches require further development and have not reached clinical trials.

Toxoplasma gondii is a single-cell intracellular protozoan parasite of the phylum apicomplexa. Its primary hosts are felines, and only in them it can go through the sexual stages of its life cycle. However, as secondary hosts it can infect many warm-blooded organisms, including humans. In humans as in rodents, after the host contracts the parasite (typically after ingestion of infectious tissue cysts or oocysts), the parasite differentiates into the fast-replicating tachyzoite stage. Toxoplasma gondii tachyzoites invade nucleated host cells by active penetration and establish a vacuole within which they replicate by endodyogeny. The tachyzoites travel through the intestinal epithelium, and by both “hitch-hiking” on immune cells and by mobilizing itself autonomously, they reach distal tissues, breach the blood brain barrier and spread in the brain [Harker 2015, Parasite Immunol. 37(3):141-9]. Thus, the tachyzoites enter the circulation and disseminate to secondary tissues. Replication is critical for dissemination and for reaching distal tissues during the acute stage of infection. Once inside the unique environment of the brain, T. gondii penetrates cells in the brain (primarily neurons, but also glial cells in lower proportions) and following immune pressure, it differentiates to the latent bradyzoite stage, and resides in cytoplasmic intercellular cysts. This characterizes a chronic infection (Cabral et al. 2016, PLoS Pathog. 12(2):e1005447). Tissue cysts harbouring bradyzoites persist for the lifetime of the host, while multiplying very slowly and having a quiescent metabolic program (Parasite Immunol. 2015, 37(3):141-9. “Toxoplasma gondii dissemination: a parasite's journey through the infected host”).

Although T. gondii infects an estimated one third of the world population, infection remains asymptomatic in healthy humans (Montoya, J. G. & Liesenfeld, O. 2004) and is primarily a risk only for individuals with irregularly compromised immune systems. Most importantly, during infection T. gondii secretes proteins into the host's cells, both during cell invasion and while intracellular. T. gondii has three types of electrodense secretory organelles: micronemes, rhoptries, and dense granules. Host cell invasion is mediated by the sequential secretion of the contents of all three organelles, which are exocytosed from the apical region when the parasite invades the host cell and when it resides inside it (Dlugonska, H. 2008). Micronemes are involved in the attachment and penetration of T. gondii, while rhoptries are required for creating a transient structure, moving junction and then the establishment of the PV. Rhoptry proteins are secreted upon initial contact with the host in a process termed “kiss and spit” (Boothroyd, J. C. et al., 2008). Dense granules secrete proteins throughout most of the parasite stages. The secretion process coincides with the formation of intravacuolar network and continues during the intracellular residence of T. gondii (Dlugonska, H. 2008; Carruthers, V. B. & Sibley, L. D. 1997).

Additional background art includes Koshy, A. A. et al. 2010; U.S. Pat. No. 8,673,289; US20120045477 Al; Lodoen M. B., et al. 2010. Cellular Microbiology, 12: 55-66.

SUMMARY OF THE INVENTION

According to an aspect of some embodiments of the present invention there is provided a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein the heterologous polynucleotide is operably linked to a promoter for directing transcription of the heterologous polynucleotide in a Toxoplasma, wherein the promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that the promoter is not a Toxofilin promoter.

According to an aspect of some embodiments of the present invention there is provided a nucleic acid construct system comprising at least two nucleic acid constructs, wherein a first nucleic acid construct of the at least two nucleic acid constructs is the nucleic acid construct of some embodiments of the invention, and a second nucleic construct of the at least two nucleic acid constructs comprises a polynucleotide encoding a selectable marker.

According to an aspect of some embodiments of the present invention there is provided a Toxoplasma transformed with the nucleic acid construct of some embodiments of the invention or with the nucleic acid construct system of some embodiments of the invention.

According to an aspect of some embodiments of the present invention there is provided a pharmaceutical composition comprising the Toxoplasma of some embodiments of the invention, and a pharmaceutically acceptable carrier.

According to an aspect of some embodiments of the present invention there is provided a method of administering a protein-of-interest into a central nervous system of a subject, the method comprising: administering to the subject the Toxoplasma of some embodiments of the invention or the pharmaceutical composition of some embodiments of the invention, thereby administering the protein-of-interest to the central nervous system of the subject.

According to an aspect of some embodiments of the present invention there is provided a method of treating a subject in need thereof, comprising administering to the subject the Toxoplasma of some embodiments of the invention or the pharmaceutical composition of some embodiments of the invention, wherein the subject is diagnosed with a pathology treatable by administration of the pharmaceutical polypeptide in a central nervous system of the subject, thereby treating the subject in need thereof.

According to an aspect of some embodiments of the present invention there is provided a method of treating a subject in need thereof, comprising administering to the subject a Toxoplasma comprising a nucleic acid construct which comprises a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein the heterologous polynucleotide is operably linked to a promoter for directing transcription of the heterologous polynucleotide in a Toxoplasma, wherein the subject is diagnosed with a pathology treatable by administration of the pharmaceutical polypeptide in a central nervous system of the subject, thereby treating the subject in need thereof.

According to some embodiments of the invention, the promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that the promoter is not a Toxofilin promoter.

According to some embodiments of the invention, the endogenous promoter is not of a rhoptry protein.

According to some embodiments of the invention, the Toxoplasma being not attenuated.

According to some embodiments of the invention, the Toxoplasma secreted protein is secreted from a rhoptry of the Toxoplasma.

According to some embodiments of the invention, the Toxoplasma secreted protein which is secreted from the rhoptry comprises Toxofilin and/or ROP1.

According to some embodiments of the invention, the Toxoplasma secreted protein which is secreted from the rhoptry comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:344-465.

According to some embodiments of the invention, the Toxoplasma secreted protein is a non-rhoptry protein.

According to some embodiments of the invention, the Toxoplasma secreted protein is selected from the group consisting of a microneme protein and a dense granule protein.

According to some embodiments of the invention, the Toxoplasma secreted protein is secreted from a dense granule of the Toxoplasma.

According to some embodiments of the invention, the Toxoplasma secreted protein which is secreted from the dense granule comprises a GRA16, and/or GRA24.

According to some embodiments of the invention, the Toxoplasma secreted protein is secreted from a microneme of the Toxoplasma.

According to some embodiments of the invention, the protein secreted from the microneme comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:280-322.

According to some embodiments of the invention, the protein secreted from the dense granule comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:234-279.

According to some embodiments of the invention, the Toxoplasma secreted protein comprises Toxoplasma gondii macrophage migration inhibitory factor (TgMIF).

According to some embodiments of the invention, the heterologous polynucleotide further comprises a Toxoplasma untranslated region (UTR) nucleic acid sequence upstream and/or downstream of the Toxoplasma secreted protein open reading frame.

According to some embodiments of the invention, the Toxoplasma 5′-untranslated region (5′-UTR) is placed upstream of the Toxoplasma secreted protein open reading frame.

According to some embodiments of the invention, the Toxoplasma 3′-untranslated region (3′-UTR) is placed downstream of the Toxoplasma secreted protein open reading frame.

According to some embodiments of the invention, the Toxoplasma 3′ untranslated region (3′-UTR) nucleic acid sequence is the GRA2 3′-UTR, GRA16 3′-UTR, GRA24 3′-UTR, SAG1 3′-UTR, or the DHFR 3′-UTR.

According to some embodiments of the invention, the Toxoplasma 5′ untranslated region (5′-UTR) nucleic acid sequence is the GRA2 5′-UTR, GRA16 5′-UTR, GRA24 5′-UTR, SAG1 5′-UTR, or the DHFR 5′-UTR.

According to some embodiments of the invention, the Toxoplasma endogenous promoter is the GRA2 promoter, GRA16 promoter, GRA24 promoter, SAG1 promoter, or the DHFR promoter.

According to some embodiments of the invention, the Toxoplasma untranslated region (UTR) nucleic acid sequence is the Toxofilin 3′-UTR.

According to some embodiments of the invention, the nucleic acid construct further comprises a third nucleic acid sequence encoding an inducible self-destruction element.

According to some embodiments of the invention, the third nucleic acid sequence encoding the inducible self-destruction element is comprised in the same nucleic acid construct which comprises the heterologous polynucleotide comprising the first nucleic acid sequence encoding the Toxoplasma secreted protein in frame fused upstream to the second nucleic acid sequence encoding the pharmaceutical polypeptide.

According to some embodiments of the invention, the third nucleic acid sequence encoding the inducible self-destruction element is comprised in a separate nucleic acid construct with respect to the nucleic acid construct which comprises the heterologous polynucleotide comprising the first nucleic acid sequence encoding the Toxoplasma secreted protein in frame fused upstream to the second nucleic acid sequence encoding the pharmaceutical polypeptide.

According to some embodiments of the invention, the nucleic acid construct does not comprise a Cre-recombinase coding sequence.

According to some embodiments of the invention, the nucleic acid construct does not comprise a beta (β)-lactamase (BLA) coding sequence.

According to some embodiments of the invention, the nucleic acid construct is suitable for integration into a genome of Toxoplasma.

According to some embodiments of the invention, the inducible self-destruction element is active in response to a drug.

According to some embodiments of the invention, the drug comprises an antibiotic.

According to some embodiments of the invention, the nucleic acid construct further comprises at least one in frame cleavage site which allows detachment of the pharmaceutical polypeptide from the Toxoplasma secreted protein.

According to some embodiments of the invention, the Toxoplasma is devoid of elements which facilitate propagation of the Toxoplasma in a host cell.

According to some embodiments of the invention, the Toxoplasma is devoid of virulence genes which are not necessary for delivery of the protein-of-interest into a CNS of a subject.

According to some embodiments of the invention, the heterologous polynucleotide further comprises a nucleic acid sequence encoding a selectable marker.

According to some embodiments of the invention, the selectable marker comprises chloramphenicol acetyltransferase (CAT), DHFR-TS, BLE, HXGPRT, UPRT, TK, CD, a fluorescent protein (such as GFP, YFP, RFP, mCherry or other) or an epitope tag (such as HA, Myc, Ty-1, FLAG or other).

According to some embodiments of the invention, the pharmaceutical composition is for treating a subject diagnosed with a pathology characterized by a deficient endogenous protein in a central nervous system of a subject.

According to some embodiments of the invention, the pharmaceutical composition is for treating a subject diagnosed with a pathology which is treatable by administration of the pharmaceutical polypeptide in a central nervous system of a subject.

According to some embodiments of the invention, the pharmaceutical composition further comprises an immunosuppression agent.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug prior to administration of the Toxoplasma and/or subsequent to administration of the Toxoplasma and/or concomitantly with administration of the Toxoplasma to the subject.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug prior to administration of the Toxoplasma to the subject.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug subsequent to administration of the Toxoplasma to the subject.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug concomitantly with administration of the Toxoplasma to the subject.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises a wild type amino acid sequence corresponding to the endogenous protein capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises an antibody capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises an antigen capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises a toxin capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises an enzyme, a structural polypeptide, a motility polypeptide, a regulatory polypeptide, a storage polypeptide, a signaling/ligand polypeptide, a receptor polypeptide, a sensory polypeptide, an antibody, a protein channel and/or a transport polypeptide.

According to some embodiments of the invention, administering is performed by peripheral administration.

According to some embodiments of the invention, the peripheral administration comprises intravenous administration.

According to some embodiments of the invention, the peripheral administration comprises oral administration.

According to some embodiments of the invention, administering is performed by direct administration to the central nervous system.

According to some embodiments of the invention, the deficient endogenous protein comprises a deletion, insertion, and/or substitution of at least one amino acid of the endogenous protein as compared to a wild type amino acid sequence of the endogenous protein.

According to some embodiments of the invention, the deficient endogenous protein comprises a reduced level of the endogenous protein as compared to a level of the endogenous protein in a healthy subject devoid of the pathology.

According to some embodiments of the invention, the deficient endogenous protein is absence of the endogenous protein in the subject diagnosed with the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide is Galactocerebrosidase (GALC).

According to some embodiments of the invention, the pharmaceutical polypeptide is Galactocerebrosidase (GALC) isoform 1, isoform 2, isoform 3, isoform 4 or isoform 5.

According to some embodiments of the invention, the pharmaceutical polypeptide is Methyl-CpG Binding Protein 2 (MECP2) isoform 1 or MECP2 isoform 2.

According to some embodiments of the invention, the pharmaceutical polypeptide is Glial Cell Derived Neurotrophic Factor (GDNF).

According to some embodiments of the invention, the pharmaceutical polypeptide is Glial Cell Derived Neurotrophic Factor (GDNF) isoform 1, isoform 2, isoform 3, isoform 4 or isoform 5.

According to some embodiments of the invention, the pharmaceutical polypeptide is Aspartoacylase (ASPA).

According to some embodiments of the invention, the pharmaceutical polypeptide is Survival Motor Neuron Protein (SMN1).

According to some embodiments of the invention, the pharmaceutical polypeptide is Survival Motor Neuron Protein isoform SMN, isoform SMN-delta5, isoform SMN-delta7, or isoform SMN-delta57.

According to some embodiments of the invention, the pharmaceutical polypeptide is Parkin (PARK2).

According to some embodiments of the invention, the pharmaceutical polypeptide is Parkin (PARK2) isoform 1, isoform 2, isoform 3, isoform 4, isoform 5, isoform 6, isoform 7, or isoform 8.

According to some embodiments of the invention, the pharmaceutical polypeptide is Transcription Factor E B (TFEB).

According to some embodiments of the invention, the pharmaceutical polypeptide is Transcription Factor E B (TFEB) isoform 1 or isoform 2.

According to some embodiments of the invention, the pharmaceutical polypeptide is a TALEN (TALE nuclease).

According to some embodiments of the invention, the pharmaceutical polypeptide is a TALE TF (TALE transcription factor).

According to some embodiments of the invention, the subject is diagnosed with Krabbe disease.

According to some embodiments of the invention, the subject is diagnosed with Rett syndrome.

According to some embodiments of the invention, the subject is diagnosed with Canavan disease.

According to some embodiments of the invention, the subject is diagnosed with Spinal Muscular Atrophy.

According to some embodiments of the invention, the subject is diagnosed with Parkinson's disease.

According to some embodiments of the invention, the subject is diagnosed with hypoxic/ischemic or neuroinflammatory CNS disorder.

According to some embodiments of the invention, the subject is diagnosed with Alzheimer's disease.

According to some embodiments of the invention, the subject is diagnosed with Amyotrophic Lateral Sclerosis.

According to some embodiments of the invention, the subject is diagnosed with Huntington's disease.

According to some embodiments of the invention, the subject is diagnosed with a lysosomal storage disease.

According to some embodiments of the invention, the subject is diagnosed with MECP2-duplication syndrome.

According to some embodiments of the invention, the method further comprising administering to the subject a drug capable of inducing the self-destruction element.

According to some embodiments of the invention, the method further comprising administering to the subject a molecule necessary for sustaining the Toxoplasma inside the host cell and/or body.

According to some embodiments of the invention, the molecule necessary for sustaining the Toxoplasma is an antibiotic.

According to some embodiments of the invention, the molecule necessary for sustaining the Toxoplasma is a small-molecule.

According to some embodiments of the invention, the molecule necessary for sustaining the Toxoplasma is a metabolite.

Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a schematic representation of the clinical concept of some embodiments of the invention. (1) The pharmaceutical polypeptide coding sequence of choice is fused to a Toxoplasma gondii secretable polypeptide coding sequence; (2) The nucleic acid construct is introduced into the Toxoplasma; (3) The fusion protein is expressed inside the parasite and localizes to the parasite's secretory organelle (here shown as an example, the rhoptries); (4) The parasite enters the CNS of the subject and reaches the site of pathology; (5) The protein is secreted into the subject's cells and rescues the pathological phenotype.

FIG. 2 depicts a schematic map of the construct used for the generation of therapeutic transgenic T. gondii lines based on the pGRA backbone. The nucleic acid construct comprises an open reading frame (ORF) consisting of a fusion of a therapeutic polypeptide coding sequence in frame with the T. gondii Toxofilin coding sequence and an “HA” tag. Upstream of the ORF is the endogenous 5′ UTR (untranslated region) of the Toxofilin gene (Toxofilin 5′-UTR which acts as a promoter), and downstream of the ORF is the 3′ UTR of the abundant dense granule protein GRA2 (GRA2 3′-UTR). The construct also contains a selectable marker cassette consisting of the HXGPRT gene, nested between the endogenous 5′ UTR and the 3′ UTR of DHFR-TS. Also included in the construct is a bacterial expression cassette including selectable antibiotic resistance.

FIG. 3 depicts a schematic map of the construct used for the generation of therapeutic transgenic T. gondii lines based on the pGRA backbone. The nucleic acid construct comprises an ORF consisting of a fusion of a therapeutic polypeptide coding sequence in frame with the T. gondii GRA16 coding sequence and an HA tag. Upstream of the ORF is the endogenous 5′ UTR of the GRA16 gene (GRA16 5′-UTR which acts as a promoter), and downstream of the ORF is the 3′ UTR of the abundant dense granule protein GRA2 (GRA2 3′-UTR). The construct also contains a selectable marker cassette consisted of the HXGPRT gene, nested between the endogenous 5′-UTR and the 3′-UTR of DHFR-TS. Also included in the construct is a bacterial expression cassette including selectable antibiotic resistance.

FIGS. 4A-I depict novel parasite strains within mammalian cells (HFF), wherein the parasite strains expressing the Toxofilin-fused therapeutic proteins Aspartoacylase (ASPA), Survival motor neuron protein (SMN1), Methyl-CpG Binding Protein 2 (MECP2) and Galactocerebrosidase-TAT 443 (also referred to as “mutated GALC-TAT” in the GENERAL MATERIALS AND EXPERIMENTAL METHODS section), presenting specific localization to the parasites' secretory rhoptry organelles. FIG. 4A—Schematic structure of an intracellular T. gondii, highlighting the rhoptries. Red: inner membrane complex (IMC), Blue: DNA (host cell nucleus and T. gondii nucleus), Green: rhoptry proteins; FIGS. 4B-I—Fluorescence microscopy analysis of parasites grown on HFF cells, expressing endogenously HA-tagged Toxofilin-ASPA (FIGS. 4B and 4C), HA-tagged Toxofilin-SMN1 (FIGS. 4D and 4E), HA-tagged Toxofilin-MECP2 (FIGS. 4F and 4G) and HA-tagged Toxofilin-GALC-TAT mutated (FIGS. 4H and 41) using anti-HA antibody (green in all panels), co-stained with the inner membrane complex IMC1 using anti-IMC1 antibody (red) and DAPI (blue), or shown on top of a polarized light image of the cells (grayscale). Parasites are shown in a mixed population, whereas only parasites showing green staining express the transgenic proteins. Scale bar=5 μM in all of the images shown in FIGS. 4B-I.

FIGS. 5A-I depict novel parasite strains within mammalian cells (HFF), wherein the parasite strains expressing the GRA16-fused therapeutic proteins Aspartoacylase (ASPA), Survival motor neuron protein (SMN1) and Methyl-CpG Binding Protein 2 (MECP2), presenting specific localization to the parasitophorous vacuole (PV) space, as well as to the host cell nucleus. FIG. 5A—Schematic representation of intracellular T. gondii parasites in a parasitophorous vacuole inside a host cell (fibroblast), highlighting the distribution of secreted dense granule effector proteins. Red: inner membrane complex (IMC), blue: DNA (host cell nucleus and T. gondii nuclei), yellow: dense granule secreted effector proteins, orange: parasitophorous vacuole. FIGS. 5B-I—Fluorescence microscopy analysis of parasites grown on HFF cells, expressing endogenously HA-tagged GRA16-ASPA (FIGS. 5B and 5C), HA-tagged GRA16-SMN1 (FIGS. 5D and 5E) and HA-tagged GRA16-MECP2 (FIGS. 5B-G in 100× magnification and FIGS. 5H-I in 40× magnification) using anti-HA antibody (green in all panels), co-stained with the inner membrane complex IMC1 using anti-IMC1 antibody (red) and DAPI (blue), or shown on top of a polarized light image of the cells. Parasites are shown in a mixed population, whereas only parasites showing green staining express the transgenic proteins. Scale bar=5 μM (for FIGS. 5B-G). Scale bar=20 μM (for FIGS. 5H-I).

FIGS. 6A-B are schematic illustrations of a TALE Nuclease (FIG. 6A) and TALE transcription factor (FIG. 6B) which are designed, as example, to the “TACGTACG” (SEQ ID NO: 4505) target sequence. The TALE repeats are presented according to the order of the nucleotides in the target sequence. It is noted that because of the nature of TALEs, the first nucleotide always has to be T (so it is integrated in the TAL N-Terminus and is not annotated), and the last nucleotide (in this case G) is represented in a half-monomer (so it is annotated as “Half repeat”). In order to be expressed and secreted by the Toxoplasma of some embodiments of the invention, the open reading frame (ORF) of these constructs is inserted to the nucleic acid construct of some embodiments of the invention. For the TALE_Nuc (TALE nuclease) the ORF is from the NLS until after the FokI (e.g., nucleotides 2113-4104 of the polynucleotide set forth by SEQ ID NO: 4506). For the TALE-TF (TALE Transcription Factor) the ORF is from the TALE N terminus (N-term) after the EGFP (e.g., nucleotides 2120-5005 of the polynucleotide set forth by SEQ ID NO: 4507). “TALE-TF”=TALE transcription factor; “TALEN”=TALE nuclease. “NI”, “NG”, “NN” and “HD”=monomers as described in Example 5 hereinbelow.

FIG. 7 depicts a schematic map of the constructs used for the generation of the therapeutic transgenic T. gondii lines. The nucleic acid construct comprises an open reading frame (ORF) consisting of a fusion of a therapeutic polypeptide coding sequence in frame with the T. gondii Toxofilin coding sequence and an “HA” tag. Upstream of the ORF is the endogenous 5′ UTR (untranslated region) of the Toxofilin gene (the “Toxofilin 5′-UTR”), and downstream of the ORF is the 3′ UTR of the abundant dense granule protein GRA2 (“GRA2 3′-UTR”). The construct also contains a selectable marker cassette consisting of the HXGPRT gene, DHFR-TS gene or mCherry gene, nested between the endogenous 5′ UTR and the 3′ UTR of DHFR-TS. Also included in the construct is a bacterial expression cassette including selectable antibiotic resistance, used for molecular cloning.

FIG. 8 depicts a schematic map of the construct used for the generation of the therapeutic transgenic T. gondii lines. The nucleic acid construct comprises an ORF consisting of a fusion of a therapeutic polypeptide coding sequence in frame with the T. gondii GRA16 coding sequence and an HA tag. Upstream of the ORF is the endogenous 5′ UTR of the GRA16 gene (the “GRA16 5′-UTR”), and downstream of the ORF is the 3′ UTR of the abundant dense granule protein GRA2 (“GRA2 3′-UTR”). The construct also contains a selectable marker cassette consisted of the HXGPRT gene, DHFR-TS gene or mCherry gene, nested between the endogenous 5′ UTR and the 3′ UTR of DHFR-TS. Also included in the construct is a bacterial expression cassette including selectable antibiotic resistance, used for molecular cloning.

FIGS. 9A-N depict images of transgenic parasites within mammalian cells (HFF), wherein the parasite strains expressing 12 novel Toxofilin-fused therapeutic proteins. FIG. 9A—Schematic structure of an intracellular T. gondii, highlighting the rhoptries. Magenta: inner membrane complex (IMC), cyan: DNA (host cell nucleus and T. gondii nucleus), yellow: rhoptry proteins; FIG. 9B—Representative fluorescence microscopy image of T. gondii grown in HFF cells, immunostained for the rhoptry marker ROP2/4 (yellow). Left: co-stained with DAPI (cyan), right: overlaid on a polarized-light image (grayscale). FIGS. 9C-N—images of transgenic parasites expressing the HA-tagged Toxofilin-fused therapeutic proteins: FIG. 9C—Aspartoacylase (ASPA), FIG. 9D—Aspartoacylase codon-optimized (ASPAopt), FIG. 9E—Galactocerebrosidase (GALC), FIG. 9F—Galactocerebrosidase codon-optimized (GALCopt), FIG. 9G—Galactocerebrosidase-TAT (GALC-TAT), FIG. 9H—Galactocerebrosidase-TAT 443 (GALC-TAT 443—also referred to as “mutated GALC-TAT” in the GENERAL MATERIALS AND EXPERIMENTAL METHODS section), FIG. 9I—Glial Cell Derived Neurotrophic Factor (GDNF), FIG. 9J—Methyl-CpG Binding Protein 2 (MECP2), FIG. 9K—Methyl-CpG Binding Protein 2 codon-optimized (MECP2opt), FIG. 9L—Parkin (PARK2), FIG. 9M—Survival motor neuron protein (SMN1) and FIG. 9N—Transcription Factor EB codon-optimized (TFEBopt). Example images of the parasites expressing Toxofilin-ASPAopt, Toxofilin-GALC-TAT 443, Toxofilin-GDNF, Toxofilin-MeCP2opt, Toxofilin-PARK2, Toxofilin-SMN1 and Toxofilin-TFEB show localization to the parasites' secretory rhoptry organelles. Toxofilin fusion protein are immunostained using anti-HA antibody (yellow). Left: co-stained with DAPI (cyan) and the parasite marker anti-IMC-1 (magenta), right: overlaid on a polarized-light image (grayscale). Parasites are shown in a mixed population, whereas only parasites showing yellow staining express the transgenic proteins. Scale bars=5 μM.

FIGS. 10A-J depict images of transgenic parasites within mammalian cells (HFF), wherein the parasite strains expressing 8 novel GRA16-fused therapeutic proteins. FIG. 10A—Schematic representation of intracellular T. gondii parasites in a parasitophorous vacuole inside a host cell, highlighting the distribution of secreted dense granule effector proteins. Magenta: inner membrane complex (IMC), cyan: DNA (host cell nucleus and T. gondii nuclei), yellow: dense granule secreted effector proteins, orange: parasitophorous vacuole; FIG. 10B—Representative fluorescence microscopy image of T. gondii grown in HFF cells, expressing an HA-tagged GRA16 protein and immunostained with anti-HA (yellow). Left: co-stained with DAPI (cyan), right: overlaid on a polarized-light image (grayscale). FIGS. 10C-J—Example images of transgenic parasites expressing the HA-tagged GRA16-fused therapeutic proteins: FIG. 10C—Aspartoacylase (ASPA), FIG. 10D—Survival motor neuron protein (SMN1), FIG. 10E—Galactocerebrosidase (GALC), FIG. 10F—Galactocerebrosidase-TAT (GALC-TAT), FIG. 10G—Aspartoacylase codon-optimized (ASPAopt). FIG. 10H—Galactocerebrosidase codon-optimized (GALCopt), FIG. 10I—Methyl-CpG Binding Protein 2 codon-optimized (MECP2opt) and FIG. 10J—Transcription Factor EB codon-optimized (TFEBopt). GRA16-ASPA, GRA16-SMN1, GRA16-ASPAopt, GRA16-MECP2opt and GRA16-TFEBopt show localization to the parasitophorous vacuole. GRA16-MECP2opt and GRA16-TFEBopt show also localization to the host cell nucleus. GRA16 fusion protein are immunostained using anti-HA antibody (yellow). Left: co-stained with DAPI (cyan) and the parasite marker anti-IMC-1 (magenta), right: overlaid on a polarized-light image (grayscale). Parasites are shown in a mixed population, whereas only parasites showing yellow staining express the transgenic proteins. Scale bars=5 μM.

FIGS. 11A-C— Dynamics of protein delivery to the nuclei of HFF cells by tachyzoites of the strains RH GRA16-HAstop, GRA16-MECP2opt and GRA16-TFEBopt, over time and multiplicity of infection (MOI). Infected cells and nuclei delivery were counted by automated image analysis using GE IN Cell Investigator software (GE healthcare, Chicago, Ill., USA). Graphs represent aggregated results from the 3 strains together.

FIGS. 12A-C—Representative images of in vitro-differentiated LUHMES human neuronal cells 16-22 hours after infection with tachyzoites of the T. gondii strains RH GRA16-HAstop (FIG. 12A), GRA16-MECP2opt (FIG. 12B) and GRA16-TFEBopt (FIG. 12C). GRA16 fusion protein are immunostained using an anti-HA antibody (yellow) and co-stained with DAPI (cyan) and the marker for mature neurons anti-NeuN (magenta). Insets on the left of each figure show the infected cells visualized with anti-HA only (top, yellow), anti-HA and DAPI (middle, yellow and cyan) and anti-HA and NeuN (bottom, yellow and magenta). All strains show clear secretion and targeting of the fusion proteins to the nuclei of the human neurons.

FIGS. 13A-D—Representative images of immunohistochemically stained neuron-enriched primary cultures from the cortices and hippocampi of P1 mice pups, 12 hours after infection with tachyzoites of the transgenic line RH GRA16-MECP2opt. The GRA16-MeCP2 fusion protein is immunostained using an anti-HA antibody (yellow). FIG. 13A—GRA16-MeCP2 alone (yellow). FIG. 13B—DAPI alone (cyan). FIG. 13C—merge of GRA16-MeCP2 and DAPI staining. FIG. 13D—merge of GRA16-MeCP2 (yellow), DAPI (cyan) and NeuN (magenta) overlaid on a polarized-light image (grayscale). The delivered GRA16-MeCP2opt demonstrates a characteristic pattern of co-localization with areas of condensed, heterochromatic DNA in the nuclei of the neuron, suggesting effective binding of the delivered MeCP2 to heterochromatin.

FIG. 14 is a Western blot of nuclear extracts of R306C MeCP2-mutant human LUHMES neurons infected with an MOI=1 of the RH GRA16-MECP2opt transgenic T. gondii strain, immunoprecipitated and blotted with a MeCP2-specific antibody. The blot shows two bands corresponding to the endogenous mutated MeCP2 and the T. gondii-delivered MeCP2. The T. gondii-delivered MeCP2 has higher molecular weight due to the fusion to GRA16.

FIGS. 15A-C show example images of in vitro differentiated bradyzoites of the transgenic T. gondii strain Pru GRA16-MECP2opt in HFF cells. The GRA16-MeCP2 fusion protein is immunostained using an anti-HA antibody (red). FIG. 15A—GRA16-MeCP2 alone. FIG. 15B—co-stained with the bradyzoite cyst-wall marker Dolichos Biflorus Agglutinin (DBA) (green) and DAPI (blue) showing in green the parasite cyst and blue the nuclei of the host fibroblast cells (HFF) with the HA-stained (red) GRA16-MeCP2 fusion protein within the nucleus of the host fibroblast cell containing the cyst. FIG. 15C—co-stained with DBA and overlaid on a polarized-light image (grayscale). The presented cyst shows continuous expression of GRA16-MeCP2, secretion and targeting of the fusion protein to the nucleus of the host cell at the bradyzoites stage. White arrowheads point on the nucleus of the cell containing the bradyzoite cyst, which contains the delivered protein GRA16-MeCP2.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to a nucleic acid construct for secretion of Toxoplasma secreted protein fused to a pharmaceutical polypeptide, and Toxoplasma comprising same, and, more particularly, but not exclusively, to a pharmaceutical compositions and methods of using same for treating a subject.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

The present inventors have uncovered that Toxoplasma parasites transformed with genetic constructs encoding for a heterologous polypeptide synthesize and deliver the heterologous polypeptide to mammalian cells (FIGS. 4B-I, 5B-I, 9B-N, 10B-J, 11A-C, 12A-C, 13A-D, 14 and 15A-C and the Examples section which follows). Inside the mammalian cells, the heterologous polypeptide shuttles to its region of activity in the cell where it is able to augment cellular processes related to the known functions of the endogenous pharmaceutical protein. For example, the present inventors generated Type I and Type II Toxoplasma strains which express and deliver the mammalian proteins MeCP2 and TFEB into mice and human cells, translationally fused to the Toxoplasma secreted protein GRA16, and secreting the fused therapeutic protein into the desired cellular localization (nuclei) within mammalian cells treated ex-vivo with the Toxoplasma (FIGS. 13A-D), thus proving the feasibility of the constructs, Toxoplasma and methods for specific delivery of therapeutic polypeptides into a subject and treating the subject.

According to an aspect to some embodiments of the invention, there is provided a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein the heterologous polynucleotide is operably linked to a promoter for directing transcription of the heterologous polynucleotide in a Toxoplasma, wherein the promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that the promoter is not a Toxofilin promoter.

According to some embodiments of the invention, the nucleic acid construct is suitable for expression in a Toxoplasma.

According to some embodiments of the invention, the nucleic acid construct does not comprise a Cre-recombinase coding sequence.

According to some embodiments of the invention, the nucleic acid construct does not comprise a beta (β)-lactamase (BLA) coding sequence.

According to some embodiments of the invention, the nucleic acid construct is suitable for integration into a genome of Toxoplasma.

According to some embodiments of the invention, the Toxoplasma is devoid of elements which facilitate propagation of the Toxoplasma in a host cell (e.g., elements important for evading the immune system of the host, elements essential for the production or utilization of certain metabolites, elements important for counteracting certain toxins or antibiotics), yet including an endogenous functional CPSII.

According to some embodiments of the invention, the Toxoplasma is devoid of virulence genes which are not necessary for delivery of the protein-of-interest into a CNS of a subject.

The nucleic acid construct includes a promoter sequence for directing transcription of the polynucleotide sequence in the Toxoplasma cell in a constitutive, transient, regulated or inducible manner.

As mentioned, the heterologous polynucleotide is operably linked to a promoter for directing transcription of the heterologous polynucleotide in a Toxoplasma.

A coding nucleic acid sequence is “operably linked” to a regulatory sequence (e.g., promoter) if the regulatory sequence is capable of exerting a regulatory effect on the coding sequence linked thereto.

As used herein, the term “promoter” refers to a region of DNA which lies upstream of the transcriptional initiation site of a gene to which RNA polymerase binds to initiate transcription of RNA. The promoter controls the timing and the intensity of expression of the gene, e.g., at which stage or condition in the lifetime of a parasite and/or of a host cell the gene is expressed.

According to some embodiments of the invention, the promoter is heterologous to the Toxoplasma used for expression of the nucleic acid construct.

According to some embodiments of the invention, the promoter is a constitutive promoter.

According to some embodiments of the invention, the promoter is an inducible promoter.

According to some embodiments of the invention, the promoter is a latent period-specific promoter.

According to some embodiments of the invention, the promoter is a Toxoplasma endogenous promoter with the proviso that the promoter is not a Toxofilin promoter.

According to some embodiments of the invention the promoter is not a Toxofillin endogenous promoter. It is noted that the predicted promoter of Toxofillin (predicted promoter of gene ID=TGME49_214080; SEQ ID NO:3689) contains the Toxofilin promoter used in some of the experiments of the Examples section (SEQ ID NO: 4482) and additional nucleotides upstream.

According to some embodiments the promoter does not comprise the nucleic acid sequence set forth by SEQ ID NO: 3689 and/or SEQ ID NO: 4482.

According to some embodiments of the invention, the endogenous promoter is not of a rhoptry protein.

According to some embodiments of the invention, the Toxoplasma endogenous promoter is the GRA2 promoter, GRA16 promoter, GRA24 promoter, SAG1 promoter, or the DHFR promoter.

According to some embodiments of the invention, the Toxoplasma endogenous promoter is the GRA2 promoter.

According to some embodiments of the invention, the Toxoplasma endogenous promoter is the GRA16 promoter.

According to some embodiments of the invention, the Toxoplasma endogenous promoter is the GRA24 promoter.

According to some embodiments of the invention, the Toxoplasma endogenous promoter is the SAG1 promoter.

According to some embodiments of the invention, the Toxoplasma endogenous promoter is the DHFR promoter.

Table 1 herein below lists suitable endogenous promoters which can be cloned into the nucleic acid construct of some embodiments of the invention in order to drive expression of the heterologous polynucleotide in the Toxoplasma.

TABLE 1 Suitable endogenous promoters Endogenous promoter starting end of gene name (ID), SEQ position on position on and length of ID Chromosome chromosome chromosome strand promoter sequence NO: TGME49_chrXII 6018714 6021975 − ID = TGME49_278580; 467 length = 3261 TGME49_chrXI 4645816 4647664 + ID = TGME49_315320; 468 length = 1848 TGME49_chrXI 5975725 5979863 − ID = TGME49_216670; 469 length = 4138 TGME49_chrIa 602877 607895 + ID = TGME49_293850; 470 length = 5018 TGME49_chrVIIa 1551626 1554994 + ID = TGME49_205190; 471 length = 3368 TGME49_chrVIIb 561320 563366 + ID = TGME49_263420; 472 length = 2046 TGME49_chrXII 2795162 2799102 + ID = TGME49_246485; 473 length = 3940 TGME49_chrIb 904562 908487 + ID = TGME49_208850; 474 length = 3925 TGME49_chrVIII 4449329 4451277 − ID = TGME49_271610; 475 length = 1948 TGME49_chrVIII 3044788 3047633 + ID = TGME49_274060; 476 length = 2845 TGME49_chrVIIb 3612195 3614194 + ID = TGME49_258060; 477 length = 1999 TGME49_chrXII 6549613 6551657 + ID = TGME49_277730; 478 length = 2044 TGME49_chrVIII 197364 199295 − ID = TGME49_229350; 479 length = 1931 TGME49_chrXI 5143319 5145850 + ID = TGME49_316130; 480 length = 2531 TGME49_chrVIIa 2471302 2472989 + ID = TGME49_203490; 481 length = 1687 TGME49_chrV 1117761 1121481 + ID = TGME49_213530; 482 length = 3720 TGME49_chrXII 5640983 5642416 − ID = TGME49_251880; 483 length = 1433 TGME49_chrIb 1120926 1123894 + ID = TGME49_209210; 484 length = 2968 TGME49_chrVIII 4996018 4997934 − ID = TGME49_270790; 485 length = 1916 TGME49_chrVIII 4266477 4270885 − ID = TGME49_271960; 486 length = 4408 TGME49_chrX 7250986 7254222 + ID = TGME49_275430; 487 length = 3236 TGME49_chrVIIb 3933132 3934570 + ID = TGME49_257640; 488 length = 1438 TGME49_chrIb 1207044 1211342 − ID = TGME49_209410; 489 length = 4298 TGME49_chrVIIb 3849337 3853482 + ID = TGME49_257750; 490 length = 4145 TGME49_chrVIII 706425 708192 + ID = TGME49_230230; 491 length = 1767 TGME49_chrII 2108697 2112820 + ID = TGME49_297920; 492 length = 4123 TGME49_chrIX 3678105 3679325 − ID = TGME49_290270; 493 length = 1220 TGME49_chrV 2469549 2471470 − ID = TGME49_285272; 494 length = 1921 TGME49_chrVIIb 2197522 2200500 + ID = TGME49_260500; 495 length = 2978 TGME49_chrXII 4500766 4502482 − ID = TGME49_249370; 496 length = 1716 TGME49_chrVIIa 2313521 2315991 − ID = TGME49_203705; 497 length = 2470 TGME49_chrVIIb 4993618 4998625 + ID = TGME49_255215; 498 length = 5007 TGME49_chrII 2100257 2103772 + ID = TGME49_297900; 499 length = 3515 TGME49_chrVIIa 2799113 2803405 − ID = TGME49_203135; 500 length = 4292 TGME49_chrIX 1389644 1391469 − ID = TGME49_265990; 501 length = 1825 TGME49_chrIX 5182974 5185461 − ID = TGME49_305030; 502 length = 2487 TGME49_chrVIII 50367 52586 − ID = TGME49_229140; 503 length = 2219 TGME49_chrX 3072006 3074113 − ID = TGME49_224350; 504 length = 2107 TGME49_chrXII 3203140 3205868 − ID = TGME49_247260; 505 length = 2728 TGME49_chrVI 1316502 1318224 + ID = TGME49_240550; 506 length = 1722 TGME49_chrVIIb 4903838 4908769 + ID = TGME49_255310; 507 length = 4931 TGME49_chrVIIa 689060 693095 + ID = TGME49_304760; 508 length = 4035 TGME49_chrVIII 1508960 1513678 − ID = TGME49_231625; 509 length = 4718 TGME49_chrXII 1903216 1907934 + ID = TGME49_217555; 510 length = 4718 TGME49_chrXI 6096576 6098700 − ID = TGME49_216530; 511 length = 2124 TGME49_chrXII 4300753 4303035 − ID = TGME49_249010; 512 length = 2282 TGME49_chrVIII 5298854 5300947 + ID = TGME49_270270; 513 length = 2093 TGME49_chrVIII 2184023 2186702 + ID = TGME49_232600; 514 length = 2679 TGME49_chrIV 1432984 1435042 − ID = TGME49_318300; 515 length = 2058 TGME49_chrIX 5708243 5710982 + ID = TGME49_305990; 516 length = 2739 TGME49_chrX 2689262 2692060 + ID = TGME49_224910; 517 length = 2798 TGME49_chrIX 871380 874729 − ID = TGME49_266960; 518 length = 3349 TGME49_chrIX 1580498 1583961 + ID = TGME49_265390; 519 length = 3463 TGME49_chrVI 1107433 1112442 + ID = TGME49_240250; 520 length = 5009 TGME49_chrXI 4618602 4621016 − ID = TGME49_315270; 521 length = 2414 TGME49_chrIX 1238941 1239596 − ID = TGME49_266290; 522 length = 655 TGME49_chrIb 65733 70002 − ID = TGME49_207440; 523 length = 4269 TGME49_chrVIIa 1078389 1081603 − ID = TGME49_206300; 524 length = 3214 TGME49_chrVIII 1628848 1630628 + ID = TGME49_231910; 525 length = 1780 TGME49_chrIa 556012 557885 + ID = TGME49_293780; 526 length = 1873 TGME49_chrIa 1286481 1288807 + ID = TGME49_294960; 527 length = 2326 TGME49_chrXII 2098720 2101108 − ID = TGME49_217760; 528 length = 2388 TGME49_chrIX 3356580 3358813 − ID = TGME49_289620; 529 length = 2233 TGME49_chrXII 6432210 6433693 − ID = TGME49_277920; 530 length = 1483 TGME49_chrIX 1440831 1443406 + ID = TGME49_265810; 531 length = 2575 TGME49_chrVIIb 2505068 2506652 − ID = TGME49_260150; 532 length = 1584 TGME49_chrVIIa 2513490 2515244 + ID = TGME49_203400; 533 length = 1754 TGME49_chrIX 4338786 4341883 − ID = TGME49_291680; 534 length = 3097 TGME49_chrVIII 1844203 1845704 + ID = TGME49_232085; 535 length = 1501 TGME49_chrXI 4303293 4303677 + ID = TGME49_314800; 536 length = 384 TGME49_chrVIIa 3949957 3952927 − ID = TGME49_201240; 537 length = 2970 TGME49_chrIa 1061383 1062031 − ID = TGME49_294680; 538 length = 648 TGME49_chrXI 5090593 5094613 + ID = TGME49_315950; 539 length = 4020 TGME49_chrVIIa 2441166 2446197 − ID = TGME49_203540; 540 length = 5031 TGME49_chrIX 5012648 5015438 − ID = TGME49_307605; 541 length = 2790 TGME49_chrVIIb 3906304 3910432 − ID = TGME49_257690; 542 length = 4128 TGME49_chrXII 3652730 3655440 − ID = TGME49_247980; 543 length = 2710 TGME49_chrVIII 6732568 6737516 + ID = TGME49_267990; 544 length = 4948 TGME49_chrIX 362887 364364 − ID = TGME49_267790; 545 length = 1477 TGME49_chrV 2197440 2202168 + ID = TGME49_285810; 546 length = 4728 TGME49_chrX 7360015 7363002 − ID = TGME49_207050; 547 length = 2987 TGME49_chrIb 1073856 1076422 + ID = TGME49_209150; 548 length = 2566 TGME49_chrVIIb 2747094 2748845 + ID = TGME49_259630; 549 length = 1751 TGME49_chrb 4351 6355 − ID = TGME49_207350; 550 length = 2004 TGME49_chrX 2899092 2901603 + ID = TGME49_224660; 551 length = 2511 TGME49_chrX 697594 700161 + ID = TGME49_227970; 552 length = 2567 TGME49_chrXI 2069622 2070833 − ID = TGME49_311430; 553 length = 1211 TGME49_chrVIII 2975808 2977909 + ID = TGME49_274150; 554 length = 2101 TGME49_chrVIIb 1633764 1635885 + ID = TGME49_261600; 555 length = 2121 TGME49_chrIX 4778923 4783666 − ID = TGME49_210450; 556 length = 4743 TGME49_chrXII 170916 172799 − ID = TGME49_300180; 557 length = 1883 TGME49_chrVI 903242 908079 − ID = TGME49_239760; 558 length = 4837 TGME49_chrXII 5256913 5260639 + ID = TGME49_250840; 559 length = 3726 TGME49_chrX 2609467 2612329 + ID = TGME49_224980; 560 length = 2862 TGME49_chrX 5806295 5808296 + ID = TGME49_237250; 561 length = 2001 TGME49_chrVI 548569 552854 − ID = TGME49_239320; 562 length = 4285 TGME49_chrVIIb 1456014 1458169 + ID = TGME49_261960; 563 length = 2155 TGME49_chrXII 838987 840604 + ID = TGME49_219590; 564 length = 1617 TGME49_chrIX 600361 602779 − ID = TGME49_267530; 565 length = 2418 TGME49_chrV 3072356 3074734 + ID = TGME49_283550; 566 length = 2378 TGME49_chrIV 1653702 1657375 + ID = TGME49_211630; 567 length = 3673 TGME49_chrXI 6343575 6348246 + ID = TGME49_216190; 568 length = 4671 TGME49_chrXII 3835647 3837281 − ID = TGME49_248400; 569 length = 1634 TGME49_chrVI 613254 616583 + ID = TGME49_239400; 570 length = 3329 TGME49_chrX 2864192 2865912 − ID = TGME49_224710; 571 length = 1720 TGME49_chrII 404894 406860 − ID = TGME49_221500; 572 length = 1966 TGME49_chrVIII 6364079 6366025 + ID = TGME49_268685; 573 length = 1946 TGME49_chrIX 3413082 3417820 − ID = TGME49_289730; 574 length = 4738 TGME49_chrIX 4411548 4413465 + ID = TGME49_291940; 575 length = 1917 TGME49_chrX 7395157 7398234 − ID = TGME49_207100; 576 length = 3077 TGME49_chrIX 4245187 4246860 + ID = TGME49_291330; 577 length = 1673 TGME49_chrV 1422070 1425388 + ID = TGME49_213910; 578 length = 3318 TGME49_chrIX 3766794 3768071 − ID = TGME49_290605; 579 length = 1277 TGME49_chrX 4283352 4285324 − ID = TGME49_234280; 580 length = 1972 TGME49_chrX 6956462 6958294 − ID = TGME49_215430; 581 length = 1832 TGME49_chrV 186946 188803 + ID = TGME49_220175; 582 length = 1857 TGME49_chrXII 2719770 2724408 − ID = TGME49_246182; 583 length = 4638 TGME49_chrX 7273127 7275437 − ID = TGME49_275440; 584 length = 2310 TGME49_chrVIII 2250133 2251577 + ID = TGME49_232760; 585 length = 1444 TGME49_chrIX 2113235 2114688 − ID = TGME49_264680; 586 length = 1453 TGME49_chrIb 1503624 1507993 + ID = TGME49_209880; 587 length = 4369 TGME49_chrVIIa 1653920 1656907 − ID = TGME49_205050; 588 length = 2987 TGME49_chrVIII 1614122 1617638 − ID = TGME49_231880; 589 length = 3516 TGME49_chrVIII 6823035 6824629 + ID = TGME49_200360; 590 length = 1594 TGME49_chrIV 392225 396143 + ID = TGME49_320290; 591 length = 3918 TGME49_chrXI 1725051 1727020 − ID = TGME49_311010; 592 length = 1969 TGME49_chrIX 1570813 1573290 + ID = TGME49_265410; 593 length = 2477 TGME49_chrIV 258575 263510 + ID = TGME49_320550; 594 length = 4935 TGME49_chrVIIb 3432626 3435118 + ID = TGME49_258410; 595 length = 2492 TGME49_chrX 4433471 4435962 − ID = TGME49_234510; 596 length = 2491 TGME49_chrXI 4695687 4699361 − ID = TGME49_315410; 597 length = 3674 TGME49_chrX 1944153 1947194 + ID = TGME49_225905; 598 length = 3041 TGME49_chrVIIb 2072870 2074965 − ID = TGME49_260670; 599 length = 2095 TGME49_chrXII 2651958 2655687 + ID = TGME49_246090; 600 length = 3729 TGME49_chrVIIa 1225490 1226911 + ID = TGME49_205662; 601 length = 1421 TGME49_chrVIIa 524618 528076 + ID = TGME49_304500; 602 length = 3458 TGME49_chrVIII 2901671 2903828 − ID = TGME49_233925; 603 length = 2157 TGME49_chrVIII 4715373 4717272 + ID = TGME49_271100; 604 length = 1899 TGME49_chrXI 4750836 4752746 − ID = TGME49_315480; 605 length = 1910 TGME49_chrX 3428954 3431481 − ID = TGME49_223960; 606 length = 2527 TGME49_chrIX 1195352 1197540 − ID = TGME49_266368; 607 length = 2188 TGME49_chrII 1798742 1800245 + ID = TGME49_297465; 608 length = 1503 TGME49_chrIX 6077602 6080932 − ID = TGME49_306430; 609 length = 3330 TGME49_chrVIIa 740498 744501 + ID = TGME49_206660; 610 length = 4003 TGME49_chrX 3135671 3138592 − ID = TGME49_224280; 611 length = 2921 TGME49_chrVIIb 3553741 3554846 − ID = TGME49_258140; 612 length = 1105 TGME49_chrIX 5352748 5353735 − ID = TGME49_305315; 613 length = 987 TGME49_chrVIII 4698087 4702028 − ID = TGME49_271115; 614 length = 3941 TGME49_chrIX 793986 798309 + ID = TGME49_267060; 615 length = 4323 TGME49_chrVIIb 3202590 3203934 + ID = TGME49_258760; 616 length = 1344 TGME49_chrX 379796 381741 + ID = TGME49_228350; 617 length = 1945 TGME49_chrX 4639580 4641831 + ID = TGME49_235150; 618 length = 2251 TGME49_chrIX 3458713 3461263 + ID = TGME49_289800; 619 length = 2550 TGME49_chrVIIa 2500255 2501767 − ID = TGME49_203450; 620 length = 1512 TGME49_chrXII 4692112 4694534 + ID = TGME49_249620; 621 length = 2422 TGME49_chrVIII 4351126 4354140 − ID = TGME49_271810; 622 length = 3014 TGME49_chrVIIa 1305173 1307774 − ID = TGME49_205570; 623 length = 2601 TGME49_chrXI 5710062 5711311 + ID = TGME49_217040; 624 length = 1249 TGME49_chrIa 876889 879930 − ID = TGME49_294390; 625 length = 3041 TGME49_chrVIIa 3975182 3977201 + ID = TGME49_201200; 626 length = 2019 TGME49_chrVIIb 2870084 2871524 − ID = TGME49_259220; 627 length = 1440 TGME49_chrVI 1084348 1088618 + ID = TGME49_240230; 628 length = 4270 TGME49_chrVIIb 3385721 3387496 + ID = TGME49_258490; 629 length = 1775 TGME49_chrVIIb 528457 531919 + ID = TGME49_263480; 630 length = 3462 TGME49_chrII 757384 761699 + ID = TGME49_222020; 631 length = 4315 TGME49_chrVIII 1358289 1362306 − ID = TGME49_231350; 632 length = 4017 TGME49_chrIX 2802162 2802980 − ID = TGME49_288900; 633 length = 818 TGME49_chrX 2467589 2469875 − ID = TGME49_225130; 634 length = 2286 TGME49_chrVIIb 2251666 2252571 − ID = TGME49_260460; 635 length = 905 TGME49_chrVIIa 2091486 2095749 + ID = TGME49_203950; 636 length = 4263 TGME49_chrIX 6058657 6060999 + ID = TGME49_306410; 637 length = 2342 TGME49_chrV 198241 200161 + ID = TGME49_220200; 638 length = 1920 TGME49_chrII 1356741 1359871 − ID = TGME49_222980; 639 length = 3130 TGME49_chrX 2206505 2209526 + ID = TGME49_225490; 640 length = 3021 TGME49_chrXII 2096828 2099495 + ID = TGME49_217770; 641 length = 2667 TGME49_chrVIIa 2970014 2971521 + ID = TGME49_202870; 642 length = 1507 TGME49_chrVIIb 322918 324659 − ID = TGME49_263800; 643 length = 1741 TGME49_chrVIIb 2953991 2955320 − ID = TGME49_259140; 644 length = 1329 TGME49_chrVIIa 1469449 1473570 + ID = TGME49_205320; 645 length = 4121 TGME49_chrXI 461912 464423 + ID = TGME49_309060; 646 length = 2511 TGME49_chrIX 1224097 1225515 − ID = TGME49_266320; 647 length = 1418 TGME49_chrII 2142037 2146242 + ID = TGME49_297970; 648 length = 4205 TGME49_chrVI 1042594 1045138 − ID = TGME49_240070; 649 length = 2544 TGME49_chrV 1309086 1311333 − ID = TGME49_213770; 650 length = 2247 TGME49_chrII 1023447 1025166 − ID = TGME49_222305; 651 length = 1719 TGME49_chrXI 1500417 1504291 − ID = TGME49_310640; 652 length = 3874 TGME49_chrXI 4378378 4379028 + ID = TGME49_314890; 653 length = 650 TGME49_chrX 738524 740600 + ID = TGME49_227910; 654 length = 2076 TGME49_chrIX 6045512 6047246 + ID = TGME49_306390; 655 length = 1734 TGME49_chrX 1935232 1938008 − ID = TGME49_225920; 656 length = 2776 TGME49_chrVI 1441267 1443761 − ID = TGME49_240770; 657 length = 2494 TGME49_chrVIIa 2001508 2005367 − ID = TGME49_204090; 658 length = 3859 TGME49_chrIa 654666 657455 − ID = TGME49_294025; 659 length = 2789 TGME49_chrVIIb 2174692 2176915 + ID = TGME49_260530; 660 length = 2223 TGME49_chrXII 711702 713805 + ID = TGME49_219700; 661 length = 2103 TGME49_chrIa 1304701 1306918 + ID = TGME49_295000; 662 length = 2217 TGME49_chrIX 568139 569234 + ID = TGME49_267560; 663 length = 1095 TGME49_chrVIII 5397829 5399254 − ID = TGME49_270110; 664 length = 1425 TGME49_chrXII 2844102 2846241 + ID = TGME49_246550; 665 length = 2139 TGME49_chrXII 4934926 4937491 + ID = TGME49_249900; 666 length = 2565 TGME49_chrX 4880053 4884161 + ID = TGME49_235470; 667 length = 4108 TGME49_chrXI 5868595 5871618 − ID = TGME49_216820; 668 length = 3023 TGME49_chrXII 6404251 6407186 − ID = TGME49_277940; 669 length = 2935 TGME49_chrIX 957423 959519 + ID = TGME49_266800; 670 length = 2096 TGME49_chrXII 5774989 5777401 − ID = TGME49_278900; 671 length = 2412 TGME49_chrVIII 3959751 3962176 + ID = TGME49_272450; 672 length = 2425 TGME49_chrVIII 3700675 3704469 − ID = TGME49_273030; 673 length = 3794 TGME49_chrVIIb 3532555 3534514 + ID = TGME49_258170; 674 length = 1959 TGME49_chrIX 5338645 5340540 − ID = TGME49_305290; 675 length = 1895 TGME49_chrIX 3807351 3810696 + ID = TGME49_290645; 676 length = 3345 TGME49_chrXII 5625786 5628283 + ID = TGME49_251855; 677 length = 2497 TGME49_chrVI 3004204 3006660 + ID = TGME49_244070; 678 length = 2456 TGME49_chrVIIa 3948602 3952191 + ID = TGME49_201230; 679 length = 3589 TGME49_chrVIII 15020 16940 + ID = TGME49_229005; 680 length = 1920 TGME49_chrIa 429247 432726 − ID = TGME49_293570; 681 length = 3479 TGME49_chrII 1927281 1932126 + ID = TGME49_297710; 682 length = 4845 TGME49_chrXI 2637010 2638757 + ID = TGME49_312370; 683 length = 1747 TGME49_chrXII 3469020 3473396 − ID = TGME49_247660; 684 length = 4376 TGME49_chrXI 4916157 4920214 − ID = TGME49_315700; 685 length = 4057 TGME49_chrIb 629071 630918 + ID = TGME49_208360; 686 length = 1847 TGME49_chrXII 6755827 6757330 + ID = TGME49_277050; 687 length = 1503 TGME49_chrVIIb 4411300 4413757 − ID = TGME49_256840; 688 length = 2457 TGME49_chrX 7049221 7051104 − ID = TGME49_215610; 689 length = 1883 TGME49_chrXII 6528538 6533549 + ID = TGME49_277760; 690 length = 5011 TGME49_chrVIIa 3427921 3430094 + ID = TGME49_202310; 691 length = 2173 TGME49_chrX 6689399 6691360 + ID = TGME49_215030; 692 length = 1961 TGME49_chrVI 2874483 2876334 + ID = TGME49_243900; 693 length = 1851 TGME49_chrVIII 83739 85719 − ID = TGME49_229180; 694 length = 1980 TGME49_chrIV 2119015 2122018 − ID = TGME49_210715; 695 length = 3003 TGME49_chrVIIb 3259075 3262189 + ID = TGME49_258680; 696 length = 3114 TGME49_chrV 125975 128008 + ID = TGME49_220100; 697 length = 2033 TGME49_chrVI 3354392 3358777 − ID = TGME49_244550; 698 length = 4385 TGME49_chrV 1810497 1813699 + ID = TGME49_286490; 699 length = 3202 TGME49_chrIb 1306317 1308410 + ID = TGME49_209530; 700 length = 2093 TGME49_chrV 2062700 2065738 + ID = TGME49_286000; 701 length = 3038 TGME49_chrIX 2762545 2764943 + ID = TGME49_288840; 702 length = 2398 TGME49_chrX 995784 1000191 + ID = TGME49_227350; 703 length = 4407 TGME49_chrIb 1537215 1542214 − ID = TGME49_209890; 704 length = 4999 TGME49_chrVI 2985954 2988613 + ID = TGME49_244050; 705 length = 2659 TGME49_chrXI 5187085 5189714 − ID = TGME49_316200; 706 length = 2629 TGME49_chrVIIa 2561670 2565986 + ID = TGME49_203340; 707 length = 4316 TGME49_chrV 2226315 2231159 + ID = TGME49_285790; 708 length = 4844 TGME49_chrIX 404524 405991 + ID = TGME49_267725; 709 length = 1467 TGME49_chrIX 694704 696929 + ID = TGME49_267360; 710 length = 2225 TGME49_chrXII 3777345 3780569 + ID = TGME49_248290; 711 length = 3224 TGME49_chrVIIa 3092406 3094459 − ID = TGME49_202720; 712 length = 2053 TGME49_chrXI 2455600 2459938 + ID = TGME49_312150; 713 length = 4338 TGME49_chrII 220920 223578 + ID = TGME49_221295; 714 length = 2658 TGME49_chrXII 2084169 2087144 − ID = TGME49_217730; 715 length = 2975 TGME49_chrIb 1007791 1010351 − ID = TGME49_209045; 716 length = 2560 TGME49_chrX 5265702 5266555 − ID = TGME49_236070; 717 length = 853 TGME49_chrVIIb 3457465 3460841 − ID = TGME49_258360; 718 length = 3376 TGME49_chrVIII 2192903 2195917 − ID = TGME49_232610; 719 length = 3014 TGME49_chrVIIb 1109483 1111172 + ID = TGME49_262640; 720 length = 1689 TGME49_chrX 3853657 3855793 − ID = TGME49_223430; 721 length = 2136 TGME49_chrXI 4239198 4243862 + ID = TGME49_314720; 722 length = 4664 TGME49_chrVIIb 2697869 2700279 + ID = TGME49_259710; 723 length = 2410 TGME49_chrVIIa 1471730 1473919 − ID = TGME49_205330; 724 length = 2189 TGME49_chrV 2711878 2714132 − ID = TGME49_284570; 725 length = 2254 TGME49_chrVIII 388717 391218 − ID = TGME49_229700; 726 length = 2501 TGME49_chrIX 1538973 1542213 + ID = TGME49_265455; 727 length = 3240 TGME49_chrXI 763730 767625 − ID = TGME49_309610; 728 length = 3895 TGME49_chrXI 2544365 2546425 + ID = TGME49_312250; 729 length = 2060 TGME49_chrVIII 5643590 5647253 − ID = TGME49_269730; 730 length = 3663 TGME49_chrIX 3584012 3585263 − ID = TGME49_290005; 731 length = 1251 TGME49_chrVIIa 3971108 3972217 − ID = TGME49_201215; 732 length = 1109 TGME49_chrIX 5666852 5669401 − ID = TGME49_305910; 733 length = 2549 TGME49_chrVIIa 1726778 1728368 + ID = TGME49_204540; 734 length = 1590 TGME49_chrIX 5763619 5766671 − ID = TGME49_306030; 735 length = 3052 TGME49_chrIX 5211532 5213996 − ID = TGME49_305080; 736 length = 2464 TGME49_chrII 1002441 1005482 + ID = TGME49_222270; 737 length = 3041 TGME49_chrXII 82314 83922 + ID = TGME49_300320; 738 length = 1608 TGME49_chrXI 4112813 4117560 + ID = TGME49_314470; 739 length = 4747 TGME49_chrVIII 6338649 6340670 − ID = TGME49_268740; 740 length = 2021 TGME49_chrIX 4955341 4957346 − ID = TGME49_210220; 741 length = 2005 TGME49_chrX 1176693 1177745 − ID = TGME49_226980; 742 length = 1052 TGME49_chrXII 1656412 1659890 − ID = TGME49_218240; 743 length = 3478 TGME49_chrXII 6033919 6035646 − ID = TGME49_278550; 744 length = 1727 TGME49_chrVIIa 2960978 2963669 − ID = TGME49_202890; 745 length = 2691 TGME49_chrXII 6087585 6092290 + ID = TGME49_278450; 746 length = 4705 TGME49_chrVIII 101229 104465 + ID = TGME49_229230; 747 length = 3236 TGME49_chrIV 1027176 1029320 − ID = TGME49_319330; 748 length = 2144 TGME49_chrV 927001 929683 + ID = TGME49_213325; 749 length = 2682 TGME49_chrVIIa 1979278 1981377 − ID = TGME49_204120; 750 length = 2099 TGME49_chrVIIa 2168400 2170024 − ID = TGME49_203875; 751 length = 1624 TGME49_chrV 805784 808589 + ID = TGME49_213040; 752 length = 2805 TGME49_chrXI 3257664 3259999 + ID = TGME49_313310; 753 length = 2335 TGME49_chrXI 4225921 4227690 − ID = TGME49_314690; 754 length = 1769 TGME49_chrXI 2469249 2471186 − ID = TGME49_312160; 755 length = 1937 TGME49_chrVIIa 3069396 3071264 − ID = TGME49_202740; 756 length = 1868 TGME49_chrVIIb 3982505 3984582 − ID = TGME49_257550; 757 length = 2077 TGME49_chrVI 2352405 2356464 − ID = TGME49_242850; 758 length = 4059 TGME49_chrVIIa 1364682 1367044 − ID = TGME49_205510; 759 length = 2362 TGME49_chrIX 3290280 3294112 − ID = TGME49_289530; 760 length = 3832 TGME49_chrX 6509764 6512159 + ID = TGME49_214820; 761 length = 2395 TGME49_chrX 581261 582904 − ID = TGME49_228110; 762 length = 1643 TGME49_chrVIIb 2990065 2994627 + ID = TGME49_259040; 763 length = 4562 TGME49_chrXI 2072060 2077000 + ID = TGME49_311450; 764 length = 4940 TGME49_chrVIII 2876231 2878765 − ID = TGME49_233880; 765 length = 2534 TGME49_chrV 1940852 1943237 + ID = TGME49_286160; 766 length = 2385 TGME49_chrIb 737486 739366 + ID = TGME49_208510; 767 length = 1880 TGME49_chrX 7427442 7429460 + ID = TGME49_207180; 768 length = 2018 TGME49_chrXI 4517672 4520283 + ID = TGME49_315150; 769 length = 2611 TGME49_chrVI 2075613 2077679 − ID = TGME49_242570; 770 length = 2066 TGME49_chrXII 5792779 5795081 − ID = TGME49_278878; 771 length = 2302 TGME49_chrXI 6607068 6609847 + ID = TGME49_298630; 772 length = 2779 TGME49_chrII 1309836 1311957 + ID = TGME49_222920; 773 length = 2121 TGME49_chrVI 3254059 3255822 − ID = TGME49_244420; 774 length = 1763 TGME49_chrVI 1733335 1738338 + ID = TGME49_241840; 775 length = 5003 TGME49_chrXII 51579 55519 + ID = TGME49_300350; 776 length = 3940 TGME49_chrIX 4278507 4279338 − ID = TGME49_291580; 777 length = 831 TGME49_chrX 537261 540449 − ID = TGME49_228160; 778 length = 3188 TGME49_chrVIII 2637897 2639548 + ID = TGME49_233430; 779 length = 1651 TGME49_chrX 6320461 6322071 − ID = TGME49_214490; 780 length = 1610 TGME49_chrVIIa 1438969 1442993 + ID = TGME49_205360; 781 length = 4024 TGME49_chrIX 423314 427457 + ID = TGME49_267710; 782 length = 4143 TGME49_chrXII 3305338 3310175 − ID = TGME49_247380; 783 length = 4837 TGME49_chrV 1107121 1109784 + ID = TGME49_213510; 784 length = 2663 TGME49_chrIX 3928247 3930598 − ID = TGME49_290900; 785 length = 2351 TGME49_chrXII 1737254 1738814 − ID = TGME49_218070; 786 length = 1560 TGME49_chrX 1297593 1300223 + ID = TGME49_226840; 787 length = 2630 TGME49_chrVI 3298917 3303680 + ID = TGME49_244480; 788 length = 4763 TGME49_chrXII 681432 686187 + ID = TGME49_219730; 789 length = 4755 TGME49_chrVIIb 1154398 1159261 + ID = TGME49_262564; 790 length = 4863 TGME49_chrVIIb 2520918 2523507 + ID = TGME49_260020; 791 length = 2589 TGME49_chrVIIa 4383439 4388493 + ID = TGME49_282130; 792 length = 5054 TGME49_chrVIII 6357878 6362199 − ID = TGME49_268710; 793 length = 4321 TGME49_chrV 3062858 3064646 − ID = TGME49_283698; 794 length = 1788 TGME49_chrIb 185665 190405 + ID = TGME49_207650; 795 length = 4740 TGME49_chrXII 3113953 3117617 − ID = TGME49_247025; 796 length = 3664 TGME49_chrIV 2662136 2664273 + ID = TGME49_317705; 797 length = 2137 TGME49_chrXI 6204102 6206390 − ID = TGME49_216375; 798 length = 2288 TGME49_chrVIIa 1971451 1974609 − ID = TGME49_204130; 799 length = 3158 TGME49_chrII 1378645 1380471 − ID = TGME49_223030; 800 length = 1826 TGME49_chrX 294956 296317 − ID = TGME49_228480; 801 length = 1361 TGME49_chrVIIa 3325912 3327698 − ID = TGME49_202445; 802 length = 1786 TGME49_chrVIIa 530623 533507 + ID = TGME49_304520; 803 length = 2884 TGME49_chrV 1878530 1880133 − ID = TGME49_286265; 804 length = 1603 TGME49_chrXI 5955570 5956873 − ID = TGME49_216700; 805 length = 1303 TGME49_chrII 2094542 2097582 − ID = TGME49_297880; 806 length = 3040 TGME49_chrX 6821949 6825368 + ID = TGME49_215220; 807 length = 3419 TGME49_chrVIII 6586174 6591203 − ID = TGME49_268280; 808 length = 5029 TGME49_chrV 2346870 2349052 + ID = TGME49_285520; 809 length = 2182 TGME49_chrVIIa 3182956 3184488 − ID = TGME49_202600; 810 length = 1532 TGME49_chrII 1959873 1961931 − ID = TGME49_297730; 811 length = 2058 TGME49_chrVIII 2213367 2216028 − ID = TGME49_232660; 812 length = 2661 TGME49_chrVIII 1472593 1474572 + ID = TGME49_231590; 813 length = 1979 TGME49_chrVIIb 407034 411993 + ID = TGME49_263650; 814 length = 4959 TGME49_chrXII 6040410 6041868 + ID = TGME49_278522; 815 length = 1458 TGME49_chrVI 128832 133066 + ID = TGME49_238210; 816 length = 4234 TGME49_chrVIII 2351312 2353449 − ID = TGME49_233020; 817 length = 2137 TGME49_chrXII 3675670 3678134 + ID = TGME49_248130; 818 length = 2464 TGME49_chrXI 1751305 1754114 + ID = TGME49_311060; 819 length = 2809 TGME49_chrVIII 3820920 3824021 − ID = TGME49_272650; 820 length = 3101 TGME49_chrIX 3958197 3961023 − ID = TGME49_290940; 821 length = 2826 TGME49_chrVIII 3927306 3931495 + ID = TGME49_272500; 822 length = 4189 TGME49_chrVIIb 4557365 4559435 − ID = TGME49_256030; 823 length = 2070 TGME49_chrVIIa 3276204 3279186 − ID = TGME49_202500; 824 length = 2982 TGME49_chrVIII 6318896 6321304 − ID = TGME49_268780; 825 length = 2408 TGME49_chrVIIb 479812 483399 + ID = TGME49_263550; 826 length = 3587 TGME49_chrIX 4290283 4293221 + ID = TGME49_291620; 827 length = 2938 TGME49_chrVI 28927 31927 + ID = TGME49_238050; 828 length = 3000 TGME49_chrIV 478540 480420 − ID = TGME49_320140; 829 length = 1880 TGME49_chrVIIa 625928 629635 − ID = TGME49_304690; 830 length = 3707 TGME49_chrXI 5485338 5489618 − ID = TGME49_316670; 831 length = 4280 TGME49_chrVIIa 1539841 1542075 + ID = TGME49_205210; 832 length = 2234 TGME49_chrXII 634097 638220 + ID = TGME49_219800; 833 length = 4123 TGME49_chrV 1822851 1827597 − ID = TGME49_286465; 834 length = 4746 TGME49_chrVIII 5573023 5577518 + ID = TGME49_269850; 835 length = 4495 TGME49_chrV 688702 691280 − ID = TGME49_212880; 836 length = 2578 TGME49_chrVIIa 718101 722948 − ID = TGME49_206700; 837 length = 4847 TGME49_chrVIIb 1078623 1080134 + ID = TGME49_262690; 838 length = 1511 TGME49_chrVIII 122484 127476 + ID = TGME49_229270; 839 length = 4992 TGME49_chrVIII 1984455 1988743 + ID = TGME49_232270; 840 length = 4288 TGME49_chrIb 1635560 1637014 + ID = TGME49_321685; 841 length = 1454 TGME49_chrXII 4936100 4940316 − ID = TGME49_249890; 842 length = 4216 TGME49_chrXI 542439 545032 − ID = TGME49_309185; 843 length = 2593 TGME49_chrX 4421909 4423573 + ID = TGME49_234505; 844 length = 1664 TGME49_chrXI 6172181 6176170 − ID = TGME49_216400; 845 length = 3989 TGME49_chrX 2291510 2293010 − ID = TGME49_225350; 846 length = 1500 TGME49_chrV 1749542 1751790 + ID = TGME49_286630; 847 length = 2248 TGME49_chrVI 1319811 1322525 + ID = TGME49_240570; 848 length = 2714 TGME49_chrVIIb 229491 232296 − ID = TGME49_264030; 849 length = 2805 TGME49_chrVI 2310854 2312930 + ID = TGME49_242810; 850 length = 2076 TGME49_chrX 6502678 6507667 − ID = TGME49_214800; 851 length = 4989 TGME49_chrXI 2060339 2062705 − ID = TGME49_311400; 852 length = 2366 TGME49_chrVIII 926825 929619 + ID = TGME49_230650; 853 length = 2794 TGME49_chrXII 105272 106503 − ID = TGME49_300300; 854 length = 1231 TGME49_chrVIII 453277 455115 − ID = TGME49_229800; 855 length = 1838 TGME49_chrX 1644562 1648123 + ID = TGME49_226420; 856 length = 3561 TGME49_chrII 1517438 1521865 + ID = TGME49_297080; 857 length = 4427 TGME49_chrVIIa 4046509 4047748 − ID = TGME49_281360; 858 length = 1239 TGME49_chrX 2847812 2849682 − ID = TGME49_224740; 859 length = 1870 TGME49_chrIX 2404001 2406112 + ID = TGME49_288240; 860 length = 2111 TGME49_chrII 2059679 2062541 − ID = TGME49_297830; 861 length = 2862 TGME49_chrVI 1483766 1486135 + ID = TGME49_240870; 862 length = 2369 TGME49_chrVIII 5701192 5703410 − ID = TGME49_269670; 863 length = 2218 TGME49_chrV 3011022 3012612 + ID = TGME49_283720; 864 length = 1590 TGME49_chrV 2873814 2875242 − ID = TGME49_283900; 865 length = 1428 TGME49_chrX 2677638 2679002 − ID = TGME49_224928; 866 length = 1364 TGME49_chrVI 459221 463664 − ID = TGME49_239090; 867 length = 4443 TGME49_chrIX 2481691 2483404 + ID = TGME49_288380; 868 length = 1713 TGME49_chrXII 6336466 6338146 − ID = TGME49_278050; 869 length = 1680 TGME49_chrXI 3461726 3464489 − ID = TGME49_313530; 870 length = 2763 TGME49_chrIV 494931 499385 − ID = TGME49_320105; 871 length = 4454 TGME49_chrVIIb 3216785 3221009 + ID = TGME49_258730; 872 length = 4224 TGME49_chrIV 2387569 2389243 − ID = TGME49_301330; 873 length = 1674 TGME49_chrXII 4581992 4584975 + ID = TGME49_249510; 874 length = 2983 TGME49_chrX 764443 766659 − ID = TGME49_227870; 875 length = 2216 TGME49_chrXI 5272434 5274572 + ID = TGME49_316400; 876 length = 2138 TGME49_chrIX 907526 912198 − ID = TGME49_266910; 877 length = 4672 TGME49_chrVIII 3348738 3350248 − ID = TGME49_273620; 878 length = 1510 TGME49_chrXII 4977966 4980165 − ID = TGME49_249990; 879 length = 2199 TGME49_chrV 2971036 2974678 − ID = TGME49_283790; 880 length = 3642 TGME49_chrXII 6194501 6196639 + ID = TGME49_278250; 881 length = 2138 TGME49_chrVIIb 4886434 4890628 − ID = TGME49_255350; 882 length = 4194 TGME49_chrVIIb 1537462 1538674 − ID = TGME49_261770; 883 length = 1212 TGME49_chrIX 2673441 2676363 − ID = TGME49_288680; 884 length = 2922 TGME49_chrX 3787941 3790472 + ID = TGME49_223480; 885 length = 2531 TGME49_chrXII 3635884 3640897 − ID = TGME49_247940; 886 length = 5013 TGME49_chrVI 3491337 3495343 + ID = TGME49_244726; 887 length = 4006 TGME49_chrXII 3425901 3428625 − ID = TGME49_247580; 888 length = 2724 TGME49_chrVIIb 1660039 1663128 + ID = TGME49_261540; 889 length = 3089 TGME49_chrVI 110931 113077 − ID = TGME49_238180; 890 length = 2146 TGME49_chrXII 1569011 1573385 − ID = TGME49_218362; 891 length = 4374 TGME49_chrVIIb 3048837 3050490 − ID = TGME49_258990; 892 length = 1653 TGME49_chrVIIb 301194 305916 + ID = TGME49_263820; 893 length = 4722 TGME49_chrVIIa 4386727 4390549 − ID = TGME49_282120; 894 length = 3822 TGME49_chrIV 205415 209239 + ID = TGME49_320600; 895 length = 3824 TGME49_chrIX 281401 284597 − ID = TGME49_279315; 896 length = 3196 TGME49_chrVIIb 4247947 4250288 + ID = TGME49_257060; 897 length = 2341 TGME49_chrXI 4347593 4351033 − ID = TGME49_314850; 898 length = 3440 TGME49_chrX 1671295 1673894 − ID = TGME49_226385; 899 length = 2599 TGME49_chrXII 1898504 1900791 − ID = TGME49_217540; 900 length = 2287 TGME49_chrVI 1623501 1626197 + ID = TGME49_241130; 901 length = 2696 TGME49_chrXI 5083118 5085552 + ID = TGME49_315940; 902 length = 2434 TGME49_chrXII 1108648 1110707 − ID = TGME49_219150; 903 length = 2059 TGME49_chrXI 3691754 3696010 − ID = TGME49_313780; 904 length = 4256 TGME49_chrIX 1201055 1203450 + ID = TGME49_266360; 905 length = 2395 TGME49_chrIX 1628753 1630162 + ID = TGME49_265290; 906 length = 1409 TGME49_chrIX 5802166 5805344 + ID = TGME49_306080; 907 length = 3178 TGME49_chrV 1269324 1271922 − ID = TGME49_213730; 908 length = 2598 TGME49_chrVIII 6544943 6546577 + ID = TGME49_268320; 909 length = 1634 TGME49_chrVI 2565899 2570600 + ID = TGME49_243350; 910 length = 4701 TGME49_chrV 244725 247396 − ID = TGME49_220250; 911 length = 2671 TGME49_chrX 4253581 4254822 − ID = TGME49_234260; 912 length = 1241 TGME49_chrXII 141229 143333 + ID = TGME49_300230; 913 length = 2104 TGME49_chrX 5248755 5253245 + ID = TGME49_236050; 914 length = 4490 TGME49_chrII 1255974 1257956 − ID = TGME49_222840; 915 length = 1982 TGME49_chrVIII 1421265 1423169 − ID = TGME49_231430; 916 length = 1904 TGME49_chrVIIa 789026 794038 − ID = TGME49_206610; 917 length = 5012 TGME49_chrVI 1454696 1457473 + ID = TGME49_240810; 918 length = 2777 TGME49_chrX 4432719 4434480 + ID = TGME49_234520; 919 length = 1761 TGME49_chrIa 999746 1003574 − ID = TGME49_294610; 920 length = 3828 TGME49_chrVIIa 374254 376921 − ID = TGME49_280480; 921 length = 2667 TGME49_chrIV 146510 149451 + ID = TGME49_320670; 922 length = 2941 TGME49_chrIX 2955650 2958322 − ID = TGME49_289060; 923 length = 2672 TGME49_chrV 2283288 2285190 − ID = TGME49_285700; 924 length = 1902 TGME49_chrVIII 2619287 2621303 + ID = TGME49_233390; 925 length = 2016 TGME49_chrXI 2246218 2248260 − ID = TGME49_311740; 926 length = 2042 TGME49_chrXII 3304425 3309462 + ID = TGME49_247390; 927 length = 5037 TGME49_chrX 6822559 6826683 − ID = TGME49_215210; 928 length = 4124 TGME49_chrXI 1048590 1053342 + ID = TGME49_310100; 929 length = 4752 TGME49_chrX 1429153 1433385 + ID = TGME49_226690; 930 length = 4232 TGME49_chrIX 2602771 2606731 + ID = TGME49_288540; 931 length = 3960 TGME49_chrX 76000 78305 − ID = TGME49_200590; 932 length = 2305 TGME49_chrVI 3131474 3132802 + ID = TGME49_244240; 933 length = 1328 TGME49_chrVI 2746962 2750934 − ID = TGME49_243600; 934 length = 3972 TGME49_chrX 4869703 4872065 + ID = TGME49_235440; 935 length = 2362 TGME49_chrIa 245706 248432 − ID = TGME49_293310; 936 length = 2726 TGME49_chrVI 18291 19862 − ID = TGME49_238030; 937 length = 1571 TGME49_chrIa 1025883 1028407 + ID = TGME49_294640; 938 length = 2524 TGME49_chrXII 6329045 6330752 − ID = TGME49_278060; 939 length = 1707 TGME49_chrXI 6343575 6346044 + ID = TGME49_216200; 940 length = 2469 TGME49_chrX 5528016 5528444 − ID = TGME49_236830; 941 length = 428 TGME49_chrVIIa 4006122 4008450 + ID = TGME49_201140; 942 length = 2328 TGME49_chrXI 744895 746156 + ID = TGME49_309590; 943 length = 1261 TGME49_chrIV 777767 779444 + ID = TGME49_319700; 944 length = 1677 TGME49_chrIa 1704993 1707763 − ID = TGME49_295600; 945 length = 2770 TGME49_chrIV 251460 253297 − ID = TGME49_320580; 946 length = 1837 TGME49_chrVIIb 4543345 4545276 + ID = TGME49_256050; 947 length = 1931 TGME49_chrVI 2880063 2882722 + ID = TGME49_243920; 948 length = 2659 TGME49_chrV 2297009 2301830 − ID = TGME49_285670; 949 length = 4821 TGME49_chrIV 742966 745952 + ID = TGME49_319850; 950 length = 2986 TGME49_chrII 551419 555255 − ID = TGME49_221670; 951 length = 3836 TGME49_chrIX 903708 908281 + ID = TGME49_266900; 952 length = 4573 TGME49_chrXII 6571890 6574505 + ID = TGME49_277685; 953 length = 2615 TGME49_chrIV 2511002 2514234 + ID = TGME49_301470; 954 length = 3232 TGME49_chrX 2881882 2886012 − ID = TGME49_224680; 955 length = 4130 TGME49_chrXII 1189943 1192566 − ID = TGME49_218955; 956 length = 2623 TGME49_chrXI 1636715 1638328 + ID = TGME49_310870; 957 length = 1613 TGME49_chrV 1740838 1743872 − ID = TGME49_286650; 958 length = 3034 TGME49_chrIV 2038028 2039463 − ID = TGME49_210815; 959 length = 1435 TGME49_chrX 6246170 6248972 + ID = TGME49_214320; 960 length = 2802 TGME49_chrVIIb 460354 462837 − ID = TGME49_263590; 961 length = 2483 TGME49_chrXI 4239198 4241167 + ID = TGME49_314715; 962 length = 1969 TGME49_chrX 1747886 1749867 − ID = TGME49_226280; 963 length = 1981 TGME49_chrVIII 4872953 4877607 + ID = TGME49_270920; 964 length = 4654 TGME49_chrII 420859 424002 − ID = TGME49_221530; 965 length = 3143 TGME49_chrXI 4902639 4904888 + ID = TGME49_315690; 966 length = 2249 TGME49_chrIX 2404526 2406796 − ID = TGME49_288230; 967 length = 2270 TGME49_chrXI 5009093 5010699 − ID = TGME49_315810; 968 length = 1606 TGME49_chrVIII 6809858 6812222 − ID = TGME49_200330; 969 length = 2364 TGME49_chrVI 1973911 1974670 + ID = TGME49_242340; 970 length = 759 TGME49_chrXII 316928 321044 − ID = TGME49_299825; 971 length = 4116 TGME49_chrII 683949 688778 + ID = TGME49_221910; 972 length = 4829 TGME49_chrIb 607119 609291 − ID = TGME49_208310; 973 length = 2172 TGME49_chrXI 1717490 1721072 + ID = TGME49_311000; 974 length = 3582 TGME49_chrXI 2887262 2889295 − ID = TGME49_312650; 975 length = 2033 TGME49_chrVIIa 332983 334493 + ID = TGME49_280522; 976 length = 1510 TGME49_chrX 1531923 1536680 + ID = TGME49_226560; 977 length = 4757 TGME49_chrVIII 2626057 2627682 + ID = TGME49_233405; 978 length = 1625 TGME49_chrVIIb 1170152 1173763 − ID = TGME49_262550; 979 length = 3611 TGME49_chrIV 1941441 1943945 + ID = TGME49_211060; 980 length = 2504 TGME49_chrVIII 4447522 4450597 + ID = TGME49_271600; 981 length = 3075 TGME49_chrVIII 1965225 1967627 + ID = TGME49_232240; 982 length = 2402 TGME49_chrIX 3596648 3598874 + ID = TGME49_290040; 983 length = 2226 TGME49_chrVIIb 3968336 3973027 − ID = TGME49_257572; 984 length = 4691 TGME49_chrV 187252 190551 − ID = TGME49_220170; 985 length = 3299 TGME49_chrVIII 1274114 1276871 + ID = TGME49_231160; 986 length = 2757 TGME49_chrVIIb 4633239 4633990 − ID = TGME49_255910; 987 length = 751 TGME49_chrXII 6567740 6569055 + ID = TGME49_277690; 988 length = 1315 TGME49_chrII 605002 607207 − ID = TGME49_221710; 989 length = 2205 TGME49_chrIb 1391208 1394231 + ID = TGME49_209680; 990 length = 3023 TGME49_chrVI 468532 470265 + ID = TGME49_239120; 991 length = 1733 TGME49_chrX 2921630 2925549 − ID = TGME49_224630; 992 length = 3919 TGME49_chrVI 2799007 2803879 − ID = TGME49_243690; 993 length = 4872 TGME49_chrVI 2904927 2906963 − ID = TGME49_243940; 994 length = 2036 TGME49_chrII 466401 468740 − ID = TGME49_221585; 995 length = 2339 TGME49_chrVIII 6616283 6618113 − ID = TGME49_268240; 996 length = 1830 TGME49_chrX 5565970 5568898 − ID = TGME49_236890; 997 length = 2928 TGME49_chrXII 651262 652841 + ID = TGME49_219770; 998 length = 1579 TGME49_chrIX 2432096 2434121 + ID = TGME49_288280; 999 length = 2025 TGME49_chrXII 1636217 1640467 − ID = TGME49_218270; 1000 length = 4250 TGME49_chrVIIa 1872508 1874024 + ID = TGME49_204330; 1001 length = 1516 TGME49_chrXII 3737300 3739417 + ID = TGME49_248200; 1002 length = 2117 TGME49_chrXI 3858510 3860201 + ID = TGME49_313990; 1003 length = 1691 TGME49_chrVI 2535609 2537835 − ID = TGME49_243302; 1004 length = 2226 TGME49_chrVIII 218635 220518 + ID = TGME49_229380; 1005 length = 1883 TGME49_chrXII 5899226 5904153 + ID = TGME49_278750; 1006 length = 4927 TGME49_chrVIIb 791575 793258 − ID = TGME49_263120; 1007 length = 1683 TGME49_chrXII 965702 969227 − ID = TGME49_219370; 1008 length = 3525 TGME49_chrVIIb 2247921 2252571 − ID = TGME49_260470; 1009 length = 4650 TGME49_chrII 925169 930001 − ID = TGME49_222160; 1010 length = 4832 TGME49_chrVIII 4328122 4331040 − ID = TGME49_271870; 1011 length = 2918 TGME49_chrVIIb 4565803 4568166 − ID = TGME49_256020; 1012 length = 2363 TGME49_chrIX 401868 404259 − ID = TGME49_267730; 1013 length = 2391 TGME49_chrIV 883987 886188 + ID = TGME49_319580; 1014 length = 2201 TGME49_chrXII 3271212 3273508 − ID = TGME49_247330; 1015 length = 2296 TGME49_chrIV 1179180 1180121 − ID = TGME49_318632; 1016 length = 941 TGME49_chrIX 5904748 5906644 − ID = TGME49_306270; 1017 length = 1896 TGME49_chrVIII 2882878 2885243 + ID = TGME49_233905; 1018 length = 2365 TGME49_chrIb 319440 322320 + ID = TGME49_207830; 1019 length = 2880 TGME49_chrXI 5276064 5279392 + ID = TGME49_316410; 1020 length = 3328 TGME49_chrVIIb 4327835 4329892 − ID = TGME49_256965; 1021 length = 2057 TGME49_chrVIIa 1383664 1387009 − ID = TGME49_205480; 1022 length = 3345 TGME49_chrX 1183277 1184615 − ID = TGME49_226970; 1023 length = 1338 TGME49_chrV 3011696 3013612 − ID = TGME49_283730; 1024 length = 1916 TGME49_chrX 1531923 1533938 + ID = TGME49_226565; 1025 length = 2015 TGME49_chrX 2248390 2249697 + ID = TGME49_225420; 1026 length = 1307 TGME49_chrVIII 792105 796468 + ID = TGME49_230450; 1027 length = 4363 TGME49_chrIX 3471473 3473649 + ID = TGME49_289830; 1028 length = 2176 TGME49_chrXI 6086232 6089255 − ID = TGME49_216560; 1029 length = 3023 TGME49_chrVIII 5980059 5982851 − ID = TGME49_269232; 1030 length = 2792 TGME49_chrVIII 2023670 2028207 + ID = TGME49_232350; 1031 length = 4537 TGME49_chrXII 3641104 3645165 + ID = TGME49_247970; 1032 length = 4061 TGME49_chrVIIb 883251 885953 − ID = TGME49_262990; 1033 length = 2702 TGME49_chrIV 2626644 2631162 − ID = TGME49_237880; 1034 length = 4518 TGME49_chrIa 111397 113812 + ID = TGME49_293060; 1035 length = 2415 TGME49_chrVI 428224 431908 − ID = TGME49_239030; 1036 length = 3684 TGME49_chrVIII 2540409 2542122 − ID = TGME49_233245; 1037 length = 1713 TGME49_chrXI 5728987 5730625 + ID = TGME49_217000; 1038 length = 1638 TGME49_chrXII 4394111 4398427 − ID = TGME49_249240; 1039 length = 4316 TGME49_chrVIIa 3976204 3977892 − ID = TGME49_201210; 1040 length = 1688 TGME49_chrIa 135999 139033 − ID = TGME49_293170; 1041 length = 3034 TGME49_chrVIIb 2446322 2450162 − ID = TGME49_260220; 1042 length = 3840 TGME49_chrXI 4005065 4007884 + ID = TGME49_314330; 1043 length = 2819 TGME49_chrIV 1721858 1725651 + ID = TGME49_211430; 1044 length = 3793 TGME49_chrVI 1440256 1442654 + ID = TGME49_240780; 1045 length = 2398 TGME49_chrVIIb 2309437 2311494 + ID = TGME49_260400; 1046 length = 2057 TGME49_chrVIII 1057314 1061637 + ID = TGME49_230850; 1047 length = 4323 TGME49_chrVIIb 3104595 3106681 + ID = TGME49_258880; 1048 length = 2086 TGME49_chrIX 3553898 3558050 + ID = TGME49_289970; 1049 length = 4152 TGME49_chrVIIb 747456 750990 − ID = TGME49_263180; 1050 length = 3534 TGME49_chrIb 508499 510809 + ID = TGME49_208010; 1051 length = 2310 TGME49_chrVIII 3403939 3407719 − ID = TGME49_273560; 1052 length = 3780 TGME49_chrVIIb 2328258 2331030 − ID = TGME49_260380; 1053 length = 2772 TGME49_chrIX 5447569 5449517 + ID = TGME49_305520; 1054 length = 1948 TGME49_chrXII 4540898 4544602 − ID = TGME49_249440; 1055 length = 3704 TGME49_chrIX 1180662 1185700 − ID = TGME49_266380; 1056 length = 5038 TGME49_chrII 741431 743464 − ID = TGME49_221990; 1057 length = 2033 TGME49_chrIX 3302423 3304195 − ID = TGME49_289550; 1058 length = 1772 TGME49_chrXII 5163344 5167027 − ID = TGME49_250740; 1059 length = 3683 TGME49_chrIb 1364877 1366149 − ID = TGME49_209620; 1060 length = 1272 TGME49_chrVIIb 858403 860259 + ID = TGME49_263020; 1061 length = 1856 TGME49_chrVI 2080861 2082634 − ID = TGME49_242580; 1062 length = 1773 TGME49_chrXI 5126509 5128203 + ID = TGME49_316100; 1063 length = 1694 TGME49_chrVIIb 2142072 2145018 + ID = TGME49_260580; 1064 length = 2946 TGME49_chrXII 2685283 2687256 + ID = TGME49_246150; 1065 length = 1973 TGME49_chrVI 110307 112590 + ID = TGME49_238190; 1066 length = 2283 TGME49_chrVIII 2837478 2839433 − ID = TGME49_233830; 1067 length = 1955 TGME49_chrX 867923 871948 + ID = TGME49_227615; 1068 length = 4025 TGME49_chrIX 5071223 5073998 − ID = TGME49_304880; 1069 length = 2775 TGME49_chrVIII 2090890 2095794 − ID = TGME49_232430; 1070 length = 4904 TGME49_chrVIIb 2781631 2784134 − ID = TGME49_259550; 1071 length = 2503 TGME49_chrX 193904 195964 + ID = TGME49_228690; 1072 length = 2060 TGME49_chrIa 1059712 1062031 − ID = TGME49_294670; 1073 length = 2319 TGME49_chrVIIa 3890344 3893030 + ID = TGME49_201520; 1074 length = 2686 TGME49_chrIX 5214676 5217074 + ID = TGME49_305100; 1075 length = 2398 TGME49_chrVIIa 899877 902361 + ID = TGME49_206520; 1076 length = 2484 TGME49_chrIX 3539347 3541778 − ID = TGME49_289940; 1077 length = 2431 TGME49_chrVIIb 4528811 4530770 − ID = TGME49_256080; 1078 length = 1959 TGME49_chrVIII 110877 112644 − ID = TGME49_229250; 1079 length = 1767 TGME49_chrXI 2296765 2300817 + ID = TGME49_311810; 1080 length = 4052 TGME49_chrXI 2742958 2745345 − ID = TGME49_312500; 1081 length = 2387 TGME49_chrV 417057 419288 + ID = TGME49_220500; 1082 length = 2231 TGME49_chrVIIb 2057525 2060480 + ID = TGME49_260680; 1083 length = 2955 TGME49_chrIb 746521 750200 + ID = TGME49_208530; 1084 length = 3679 TGME49_chrX 5474968 5478116 − ID = TGME49_236650; 1085 length = 3148 TGME49_chrX 5074937 5076733 − ID = TGME49_235710; 1086 length = 1796 TGME49_chrIb 1282077 1283563 + ID = TGME49_209510; 1087 length = 1486 TGME49_chrIa 617372 619206 + ID = TGME49_293870; 1088 length = 1834 TGME49_chrX 5248755 5250532 + ID = TGME49_236040; 1089 length = 1777 TGME49_chrXII 5288046 5290319 − ID = TGME49_250860; 1090 length = 2273 TGME49_chrIX 2720225 2724939 + ID = TGME49_288750; 1091 length = 4714 TGME49_chrIX 544999 547818 + ID = TGME49_267585; 1092 length = 2819 TGME49_chrVIIa 1068023 1069996 + ID = TGME49_206310; 1093 length = 1973 TGME49_chrVI 830758 833127 + ID = TGME49_239690; 1094 length = 2369 TGME49_chrIX 2265055 2268965 − ID = TGME49_287960; 1095 length = 3910 TGME49_chrXI 6087183 6089255 − ID = TGME49_216550; 1096 length = 2072 TGME49_chrIV 2578257 2581065 + ID = TGME49_237840; 1097 length = 2808 TGME49_chrVIII 991782 995395 − ID = TGME49_230705; 1098 length = 3613 TGME49_chrII 1884186 1886034 + ID = TGME49_297643; 1099 length = 1848 TGME49_chrXI 2312050 2313267 + ID = TGME49_311830; 1100 length = 1217 TGME49_chrII 1254506 1256879 + ID = TGME49_222850; 1101 length = 2373 TGME49_chrII 766484 768700 + ID = TGME49_222030; 1102 length = 2216 TGME49_chrIX 1961088 1961769 + ID = TGME49_264850; 1103 length = 681 TGME49_chrVIII 5344269 5348104 − ID = TGME49_270200; 1104 length = 3835 TGME49_chrVI 1380775 1382606 − ID = TGME49_240660; 1105 length = 1831 TGME49_chrVIIb 1804716 1807943 + ID = TGME49_261240; 1106 length = 3227 TGME49_chrX 3382286 3386675 + ID = TGME49_224020; 1107 length = 4389 TGME49_chrXI 1908342 1912400 − ID = TGME49_311240; 1108 length = 4058 TGME49_chrVIIa 4438610 4442652 + ID = TGME49_282200; 1109 length = 4042 TGME49_chrIX 5844712 5848045 + ID = TGME49_306230; 1110 length = 3333 TGME49_chrXI 1502815 1504291 − ID = TGME49_310650; 1111 length = 1476 TGME49_chrXI 1970355 1973898 + ID = TGME49_311320; 1112 length = 3543 TGME49_chrX 2305695 2308125 + ID = TGME49_225330; 1113 length = 2430 TGME49_chrVIIb 1736562 1738490 − ID = TGME49_261460; 1114 length = 1928 TGME49_chrXI 2288840 2290926 + ID = TGME49_311790; 1115 length = 2086 TGME49_chrX 5000703 5002026 + ID = TGME49_235635; 1116 length = 1323 TGME49_chrXI 3051809 3053089 + ID = TGME49_313025; 1117 length = 1280 TGME49_chrV 1226819 1229241 − ID = TGME49_213670; 1118 length = 2422 TGME49_chrVI 1846930 1848152 + ID = TGME49_242040; 1119 length = 1222 TGME49_chrXI 5127101 5129194 − ID = TGME49_316090; 1120 length = 2093 TGME49_chrVIIa 489530 492510 + ID = TGME49_280370; 1121 length = 2980 TGME49_chrVIII 2733118 2736128 − ID = TGME49_233702; 1122 length = 3010 TGME49_chrXI 6398771 6401970 − ID = TGME49_216120; 1123 length = 3199 TGME49_chrXI 530082 533588 − ID = TGME49_309160; 1124 length = 3506 TGME49_chrVIII 428448 432358 − ID = TGME49_229750; 1125 length = 3910 TGME49_chrII 2077832 2082637 + ID = TGME49_297850; 1126 length = 4805 TGME49_chrIV 2088470 2090595 − ID = TGME49_210770; 1127 length = 2125 TGME49_chrIV 1112801 1114995 − ID = TGME49_318742; 1128 length = 2194 TGME49_chrVIII 2694512 2696420 + ID = TGME49_233530; 1129 length = 1908 TGME49_chrIb 1392188 1394786 − ID = TGME49_209650; 1130 length = 2598 TGME49_chrV 469162 470010 + ID = TGME49_220580; 1131 length = 848 TGME49_chrIX 2034098 2036991 + ID = TGME49_264770; 1132 length = 2893 TGME49_chrVIII 2855966 2857966 − ID = TGME49_233850; 1133 length = 2000 TGME49_chrXI 1595350 1597733 + ID = TGME49_310798; 1134 length = 2383 TGME49_chrIX 5541500 5543417 + ID = TGME49_305750; 1135 length = 1917 TGME49_chrIX 4142523 4144608 + ID = TGME49_291130; 1136 length = 2085 TGME49_chrVIIb 790933 792672 + ID = TGME49_263110; 1137 length = 1739 TGME49_chrVIIa 2210477 2211546 − ID = TGME49_203815; 1138 length = 1069 TGME49_chrVIII 4063764 4065564 + ID = TGME49_272340; 1139 length = 1800 TGME49_chrIX 862193 864770 + ID = TGME49_266970; 1140 length = 2577 TGME49_chrX 6005350 6009045 − ID = TGME49_237585; 1141 length = 3695 TGME49_chrIV 812682 816552 − ID = TGME49_319650; 1142 length = 3870 TGME49_chrIV 1351025 1353144 + ID = TGME49_318410; 1143 length = 2119 TGME49_chrVIIb 628035 632181 + ID = TGME49_263323; 1144 length = 4146 TGME49_chrII 464340 467546 + ID = TGME49_221590; 1145 length = 3206 TGME49_chrVIIa 2353189 2355787 − ID = TGME49_203682; 1146 length = 2598 TGME49_chrIa 1365331 1367979 + ID = TGME49_295060; 1147 length = 2648 TGME49_chrXI 3086379 3090390 + ID = TGME49_313090; 1148 length = 4011 TGME49_chrII 639786 644118 + ID = TGME49_221870; 1149 length = 4332 TGME49_chrIV 1283541 1287463 − ID = TGME49_318490; 1150 length = 3922 TGME49_chrX 2544948 2548532 − ID = TGME49_225070; 1151 length = 3584 TGME49_chrVIIb 541912 545460 − ID = TGME49_263470; 1152 length = 3548 TGME49_chrIX 3591560 3593074 − ID = TGME49_290020; 1153 length = 1514 TGME49_chrX 3928163 3932517 − ID = TGME49_212310; 1154 length = 4354 TGME49_chrVIIb 4701292 4702972 − ID = TGME49_255720; 1155 length = 1680 TGME49_chrVIII 5506593 5510411 + ID = TGME49_269940; 1156 length = 3818 TGME49_chrIV 592700 595047 + ID = TGME49_320005; 1157 length = 2347 TGME49_chrVIIb 4519629 4521475 − ID = TGME49_256100; 1158 length = 1846 TGME49_chrIa 1848533 1850781 − ID = TGME49_295320; 1159 length = 2248 TGME49_chrX 3761112 3762929 − ID = TGME49_223530; 1160 length = 1817 TGME49_chrVIII 3839250 3840966 − ID = TGME49_272620; 1161 length = 1716 TGME49_chrX 5533324 5536592 + ID = TGME49_236850; 1162 length = 3268 TGME49_chrX 5233291 5235370 − ID = TGME49_235990; 1163 length = 2079 TGME49_chrIb 1816564 1818369 + ID = TGME49_321430; 1164 length = 1805 TGME49_chrXI 3327009 3329669 + ID = TGME49_313380; 1165 length = 2660 TGME49_chrIX 3363488 3365112 + ID = TGME49_289650; 1166 length = 1624 TGME49_chrV 287641 288269 − ID = TGME49_220310; 1167 length = 628 TGME49_chrII 2077832 2079808 + ID = TGME49_297845; 1168 length = 1976 TGME49_chrVIIb 3657735 3659476 + ID = TGME49_258000; 1169 length = 1741 TGME49_chrIX 2039013 2043206 + ID = TGME49_264760; 1170 length = 4193 TGME49_chrXII 6988840 6990981 + ID = TGME49_276810; 1171 length = 2141 TGME49_chrIX 3612365 3615024 − ID = TGME49_290160; 1172 length = 2659 TGME49_chrIa 1259545 1263126 − ID = TGME49_294898; 1173 length = 3581 TGME49_chrXI 6165715 6166848 + ID = TGME49_216415; 1174 length = 1133 TGME49_chrIX 3511489 3512915 − ID = TGME49_289890; 1175 length = 1426 TGME49_chrIX 1748283 1752414 + ID = TGME49_265130; 1176 length = 4131 TGME49_chrIV 1015278 1019035 + ID = TGME49_319340; 1177 length = 3757 TGME49_chrVI 905412 908079 − ID = TGME49_239770; 1178 length = 2667 TGME49_chrXI 570018 574932 − ID = TGME49_309220; 1179 length = 4914 TGME49_chrVIII 2228983 2231436 + ID = TGME49_232690; 1180 length = 2453 TGME49_chrXI 3756375 3758818 + ID = TGME49_313870; 1181 length = 2443 TGME49_chrXI 1683330 1684845 − ID = TGME49_310940; 1182 length = 1515 TGME49_chrIb 802516 804677 − ID = TGME49_208580; 1183 length = 2161 TGME49_chrV 3073350 3075701 − ID = TGME49_283580; 1184 length = 2351 TGME49_chrIX 2433199 2434876 − ID = TGME49_288270; 1185 length = 1677 TGME49_chrVIII 5247499 5249101 + ID = TGME49_270360; 1186 length = 1602 TGME49_chrIa 538347 541224 + ID = TGME49_293740; 1187 length = 2877 TGME49_chrXI 1034402 1037980 − ID = TGME49_310055; 1188 length = 3578 TGME49_chrVIII 4273765 4277392 + ID = TGME49_271930; 1189 length = 3627 TGME49_chrX 3942210 3943072 + ID = TGME49_212280; 1190 length = 862 TGME49_chrXI 6427213 6429335 − ID = TGME49_216060; 1191 length = 2122 TGME49_chrVIII 5776984 5780816 − ID = TGME49_269470; 1192 length = 3832 TGME49_chrVI 1334066 1335457 + ID = TGME49_240600; 1193 length = 1391 TGME49_chrVIIa 4234959 4237402 + ID = TGME49_281640; 1194 length = 2443 TGME49_chrV 1240541 1242474 + ID = TGME49_213700; 1195 length = 1933 TGME49_chrX 1079054 1081448 − ID = TGME49_227140; 1196 length = 2394 TGME49_chrXII 2362341 2363912 − ID = TGME49_245540; 1197 length = 1571 TGME49_chrVIIb 4735950 4738492 − ID = TGME49_255690; 1198 length = 2542 TGME49_chrVIIb 215535 217628 − ID = TGME49_264060; 1199 length = 2093 TGME49_chrXI 3767685 3770308 + ID = TGME49_313880; 1200 length = 2623 TGME49_chrVIIb 382525 387001 − ID = TGME49_263710; 1201 length = 4476 TGME49_chrVIII 3764146 3769011 − ID = TGME49_272730; 1202 length = 4865 TGME49_chrVIII 2518242 2523170 + ID = TGME49_233230; 1203 length = 4928 TGME49_chrX 2512981 2514745 + ID = TGME49_225105; 1204 length = 1764 TGME49_chrX 1747337 1749496 + ID = TGME49_226270; 1205 length = 2159 TGME49_chrXI 2556450 2561384 + ID = TGME49_312280; 1206 length = 4934 TGME49_chrXI 1508511 1511130 + ID = TGME49_310670; 1207 length = 2619 TGME49_chrX 1357073 1358633 − ID = TGME49_226800; 1208 length = 1560 TGME49_chrXII 1856018 1859951 − ID = TGME49_217460; 1209 length = 3933 TGME49_chrVI 1032113 1035230 + ID = TGME49_240060; 1210 length = 3117 TGME49_chrVIIb 4750240 4753174 − ID = TGME49_255660; 1211 length = 2934 TGME49_chrIV 2488322 2491013 + ID = TGME49_301450; 1212 length = 2691 TGME49_chrVIIa 2399437 2401178 + ID = TGME49_203610; 1213 length = 1741 TGME49_chrIV 717427 720591 − ID = TGME49_319870; 1214 length = 3164 TGME49_chrIX 633939 636510 + ID = TGME49_267450; 1215 length = 2571 TGME49_chrII 1064277 1067130 − ID = TGME49_222350; 1216 length = 2853 TGME49_chrX 6587512 6589629 − ID = TGME49_214910; 1217 length = 2117 TGME49_chrVIIb 1100273 1103123 + ID = TGME49_262650; 1218 length = 2850 TGME49_chrX 4019693 4021700 − ID = TGME49_212150; 1219 length = 2007 TGME49_chrIV 910057 912578 + ID = TGME49_319560; 1220 length = 2521 TGME49_chrXI 5954623 5956672 + ID = TGME49_216680; 1221 length = 2049 TGME49_chrVIIb 936733 939153 + ID = TGME49_262900; 1222 length = 2420 TGME49_chrIX 2624481 2626169 + ID = TGME49_288580; 1223 length = 1688 TGME49_chrX 6117985 6120211 + ID = TGME49_214220; 1224 length = 2226 TGME49_chrIX 4670575 4671677 − ID = TGME49_292310; 1225 length = 1102 TGME49_chrVIIa 1586701 1588039 + ID = TGME49_205140; 1226 length = 1338 TGME49_chrV 343813 347336 − ID = TGME49_220380; 1227 length = 3523 TGME49_chrVIIa 2824543 2828105 − ID = TGME49_203060; 1228 length = 3562 TGME49_chrVI 2842072 2843767 − ID = TGME49_243750; 1229 length = 1695 TGME49_chrXII 5901664 5905896 − ID = TGME49_278757; 1230 length = 4232 TGME49_chrIX 864169 866128 − ID = TGME49_266980; 1231 length = 1959 TGME49_chrV 405382 408887 − ID = TGME49_220470; 1232 length = 3505 TGME49_chrVIIb 2512076 2514420 − ID = TGME49_260140; 1233 length = 2344 TGME49_chrVI 2098336 2100722 − ID = TGME49_242600; 1234 length = 2386 TGME49_chrX 1508884 1511053 − ID = TGME49_226610; 1235 length = 2169 TGME49_chrVIIa 2043666 2046086 + ID = TGME49_204020; 1236 length = 2420 TGME49_chrVIIb 1030528 1035441 + ID = TGME49_262760; 1237 length = 4913 TGME49_chrIa 906891 908355 − ID = TGME49_294420; 1238 length = 1464 TGME49_chrIX 3949096 3950443 − ID = TGME49_290925; 1239 length = 1347 TGME49_chrV 2021160 2025024 + ID = TGME49_286060; 1240 length = 3864 TGME49_chrXI 3334286 3335654 − ID = TGME49_313385; 1241 length = 1368 TGME49_chrIX 4592337 4595459 − ID = TGME49_292170; 1242 length = 3122 TGME49_chrXII 883327 885042 − ID = TGME49_219530; 1243 length = 1715 TGME49_chrVIIa 646040 650529 + ID = TGME49_304720; 1244 length = 4489 TGME49_chrXII 2582968 2583778 + ID = TGME49_245995; 1245 length = 810 TGME49_chrVIIa 1492534 1497097 + ID = TGME49_205280; 1246 length = 4563 TGME49_chrVIII 6529292 6532178 − ID = TGME49_268340; 1247 length = 2886 TGME49_chrX 1775473 1776642 − ID = TGME49_226240; 1248 length = 1169 TGME49_chrX 3282886 3287547 + ID = TGME49_224160; 1249 length = 4661 TGME49_chrXI 6397920 6400037 + ID = TGME49_216090; 1250 length = 2117 TGME49_chrVI 2706529 2711143 + ID = TGME49_243545; 1251 length = 4614 TGME49_chrXI 416696 419057 − ID = TGME49_308980; 1252 length = 2361 TGME49_chrIb 1342257 1346867 + ID = TGME49_209580; 1253 length = 4610 TGME49_chrX 5509755 5511547 − ID = TGME49_236790; 1254 length = 1792 TGME49_chrXI 463158 465197 − ID = TGME49_309050; 1255 length = 2039 TGME49_chrVI 256977 258317 − ID = TGME49_238505; 1256 length = 1340 TGME49_chrX 6916813 6920734 − ID = TGME49_215343; 1257 length = 3921 TGME49_chrXII 4789347 4790800 + ID = TGME49_249770; 1258 length = 1453 TGME49_chrXII 2221509 2225506 − ID = TGME49_217910; 1259 length = 3997 TGME49_chrXII 635109 638817 − ID = TGME49_219810; 1260 length = 3708 TGME49_chrX 996966 1001699 − ID = TGME49_227360; 1261 length = 4733 TGME49_chrXII 4759357 4761502 − ID = TGME49_249720; 1262 length = 2145 TGME49_chrVIII 880481 882435 − ID = TGME49_230580; 1263 length = 1954 TGME49_chrVIIa 2393820 2395507 − ID = TGME49_203630; 1264 length = 1687 TGME49_chrX 3969673 3972540 − ID = TGME49_212230; 1265 length = 2867 TGME49_chrVIIa 3730718 3732764 + ID = TGME49_201870; 1266 length = 2046 TGME49_chrVIII 1001169 1003387 + ID = TGME49_230820; 1267 length = 2218 TGME49_chrIX 4600674 4601980 − ID = TGME49_292190; 1268 length = 1306 TGME49_chrIV 1318793 1321000 − ID = TGME49_318460; 1269 length = 2207 TGME49_chrXII 5008645 5010570 − ID = TGME49_250050; 1270 length = 1925 TGME49_chrVIII 2821108 2824516 + ID = TGME49_233820; 1271 length = 3408 TGME49_chrVIIa 945242 947003 + ID = TGME49_206470; 1272 length = 1761 TGME49_chrVIIa 618512 620275 − ID = TGME49_304670; 1273 length = 1763 TGME49_chrXI 5431083 5433154 − ID = TGME49_316610; 1274 length = 2071 TGME49_chrXI 3894915 3897284 + ID = TGME49_314042; 1275 length = 2369 TGME49_chrVI 613785 617334 − ID = TGME49_239885; 1276 length = 3549 TGME49_chrXII 6080645 6082084 + ID = TGME49_278470; 1277 length = 1439 TGME49_chrXII 4530057 4533822 − ID = TGME49_249425; 1278 length = 3765 TGME49_chrVIIb 4983552 4986683 − ID = TGME49_255240; 1279 length = 3131 TGME49_chrIX 6162509 6166258 + ID = TGME49_306540; 1280 length = 3749 TGME49_chrVIII 1191790 1195369 − ID = TGME49_231000; 1281 length = 3579 TGME49_chrVIIb 2539671 2543923 − ID = TGME49_260000; 1282 length = 4252 TGME49_chrVIIb 849810 852648 − ID = TGME49_263060; 1283 length = 2838 TGME49_chrVIIb 648112 651155 − ID = TGME49_263300; 1284 length = 3043 TGME49_chrIX 3384763 3389725 + ID = TGME49_289710; 1285 length = 4962 TGME49_chrIV 1667704 1671687 − ID = TGME49_211610; 1286 length = 3983 TGME49_chrVI 3370670 3372867 − ID = TGME49_244570; 1287 length = 2197 TGME49_chrIa 1384531 1387176 − ID = TGME49_295070; 1288 length = 2645 TGME49_chrII 1380736 1382666 + ID = TGME49_223045; 1289 length = 1930 TGME49_chrVIIa 4051293 4053186 − ID = TGME49_281370; 1290 length = 1893 TGME49_chrX 3955985 3958323 + ID = TGME49_212250; 1291 length = 2338 TGME49_chrVI 320087 321893 − ID = TGME49_238930; 1292 length = 1806 TGME49_chrV 1821412 1825437 + ID = TGME49_286450; 1293 length = 4025 TGME49_chrX 4558668 4561661 − ID = TGME49_234950; 1294 length = 2993 TGME49_chrIX 1512833 1516330 + ID = TGME49_265510; 1295 length = 3497 TGME49_chrVIII 6794045 6796697 + ID = TGME49_200320; 1296 length = 2652 TGME49_chrX 6978264 6981039 + ID = TGME49_215490; 1297 length = 2775 TGME49_chrX 2174211 2176205 − ID = TGME49_225540; 1298 length = 1994 TGME49_chrVIII 1298224 1302758 + ID = TGME49_231180; 1299 length = 4534 TGME49_chrII 2142882 2147668 − ID = TGME49_297960; 1300 length = 4786 TGME49_chrXII 3433690 3435922 + ID = TGME49_247600; 1301 length = 2232 TGME49_chrVIIa 2317501 2320428 − ID = TGME49_203700; 1302 length = 2927 TGME49_chrXII 6674607 6677822 − ID = TGME49_277490; 1303 length = 3215 TGME49_chrXI 4233721 4237966 − ID = TGME49_314700; 1304 length = 4245 TGME49_chrIV 425592 427430 − ID = TGME49_320230; 1305 length = 1838 TGME49_chrVIIa 2514862 2517330 − ID = TGME49_203420; 1306 length = 2468 TGME49_chrIX 4579461 4584034 − ID = TGME49_292140; 1307 length = 4573 TGME49_chrXII 5609336 5612206 + ID = TGME49_251850; 1308 length = 2870 TGME49_chrVIIb 2348892 2349464 + ID = TGME49_260330; 1309 length = 572 TGME49_chrVI 1829041 1831040 − ID = TGME49_242010; 1310 length = 1999 TGME49_chrVIII 2298908 2301088 + ID = TGME49_232970; 1311 length = 2180 TGME49_chrVIIb 5051588 5052399 + ID = TGME49_255175; 1312 length = 811 TGME49_chrX 1835017 1837256 − ID = TGME49_226068; 1313 length = 2239 TGME49_chrXI 3842477 3844120 − ID = TGME49_313960; 1314 length = 1643 TGME49_chrVIIb 821627 824086 − ID = TGME49_263085; 1315 length = 2459 TGME49_chrIV 250795 252483 + ID = TGME49_320570; 1316 length = 1688 TGME49_chrX 2164468 2166075 − ID = TGME49_225555; 1317 length = 1607 TGME49_chrX 1105074 1106948 − ID = TGME49_227070; 1318 length = 1874 TGME49_chrVIIb 1404269 1407193 + ID = TGME49_262050; 1319 length = 2924 TGME49_chrIX 599004 602300 + ID = TGME49_267520; 1320 length = 3296 TGME49_chrVIIa 3270410 3274311 − ID = TGME49_202510; 1321 length = 3901 TGME49_chrVIII 3516693 3521323 + ID = TGME49_273410; 1322 length = 4630 TGME49_chrV 2626675 2628503 + ID = TGME49_284670; 1323 length = 1828 TGME49_chrX 7344849 7347942 − ID = TGME49_207020; 1324 length = 3093 TGME49_chrVIIa 1741358 1745785 + ID = TGME49_204500; 1325 length = 4427 TGME49_chrXI 4646243 4648666 − ID = TGME49_315310; 1326 length = 2423 TGME49_chrVIIb 4281282 4283353 + ID = TGME49_257010; 1327 length = 2071 TGME49_chrIb 1755720 1757922 + ID = TGME49_321520; 1328 length = 2202 TGME49_chrX 6940384 6941995 + ID = TGME49_215400; 1329 length = 1611 TGME49_chrVI 1108072 1112890 − ID = TGME49_240243; 1330 length = 4818 TGME49_chrXII 4472490 4474867 − ID = TGME49_249340; 1331 length = 2377 TGME49_chrVIIa 970566 973439 − ID = TGME49_206450; 1332 length = 2873 TGME49_chrIb 601001 603218 + ID = TGME49_208300; 1333 length = 2217 TGME49_chrIX 5762838 5764549 + ID = TGME49_306035; 1334 length = 1711 TGME49_chrIX 653845 657554 − ID = TGME49_267440; 1335 length = 3709 TGME49_chrX 2967494 2971910 + ID = TGME49_224570; 1336 length = 4416 TGME49_chrVIII 5286926 5289744 − ID = TGME49_270310; 1337 length = 2818 TGME49_chrVIII 1877930 1881330 + ID = TGME49_232130; 1338 length = 3400 TGME49_chrXI 852387 855185 − ID = TGME49_309865; 1339 length = 2798 TGME49_chrXI 6261741 6265340 − ID = TGME49_216280; 1340 length = 3599 TGME49_chrX 2712114 2714287 − ID = TGME49_224890; 1341 length = 2173 TGME49_chrXII 2592707 2596028 − ID = TGME49_246010; 1342 length = 3321 TGME49_chrX 1673837 1675489 + ID = TGME49_226380; 1343 length = 1652 TGME49_chrXII 4784125 4785752 − ID = TGME49_249750; 1344 length = 1627 TGME49_chrVIIb 1379649 1382568 + ID = TGME49_262090; 1345 length = 2919 TGME49_chrVIIb 292075 294154 − ID = TGME49_263850; 1346 length = 2079 TGME49_chrXII 2582968 2585062 + ID = TGME49_246000; 1347 length = 2094 TGME49_chrIX 5480897 5483034 − ID = TGME49_305580; 1348 length = 2137 TGME49_chrIX 678959 682427 + ID = TGME49_267370; 1349 length = 3468 TGME49_chrIX 1283348 1288325 − ID = TGME49_266130; 1350 length = 4977 TGME49_chrXI 6528191 6531898 + ID = TGME49_215910; 1351 length = 3707 TGME49_chrVIIb 4536725 4538969 + ID = TGME49_256060; 1352 length = 2244 TGME49_chrIX 800121 801864 + ID = TGME49_267050; 1353 length = 1743 TGME49_chrXI 2857820 2862733 + ID = TGME49_312635; 1354 length = 4913 TGME49_chrVIIa 2173780 2176161 − ID = TGME49_203870; 1355 length = 2381 TGME49_chrV 1761372 1763556 + ID = TGME49_286610; 1356 length = 2184 TGME49_chrVIII 2657912 2660930 + ID = TGME49_233450; 1357 length = 3018 TGME49_chrVIIa 2656175 2659506 + ID = TGME49_203230; 1358 length = 3331 TGME49_chrVIIb 3927316 3929847 − ID = TGME49_257670; 1359 length = 2531 TGME49_chrIX 2429266 2431241 − ID = TGME49_288265; 1360 length = 1975 TGME49_chrVIII 2207468 2209626 − ID = TGME49_232650; 1361 length = 2158 TGME49_chrIV 482747 486460 − ID = TGME49_320130; 1362 length = 3713 TGME49_chrVIIb 1792513 1796589 − ID = TGME49_261300; 1363 length = 4076 TGME49_chrX 6083410 6086247 + ID = TGME49_214180; 1364 length = 2837 TGME49_chrX 6748004 6750095 − ID = TGME49_215080; 1365 length = 2091 TGME49_chrX 4919793 4924423 − ID = TGME49_235500; 1366 length = 4630 TGME49_chrVIIa 3365745 3369481 − ID = TGME49_202390; 1367 length = 3736 TGME49_chrVIIa 88266 91194 + ID = TGME49_280780; 1368 length = 2928 TGME49_chrXII 6725504 6728703 − ID = TGME49_277080; 1369 length = 3199 TGME49_chrVIII 5699778 5702719 + ID = TGME49_269660; 1370 length = 2941 TGME49_chrIV 101470 104091 + ID = TGME49_320740; 1371 length = 2621 TGME49_chrXI 4317799 4319648 − ID = TGME49_314820; 1372 length = 1849 TGME49_chrIb 1727396 1729180 − ID = TGME49_321570; 1373 length = 1784 TGME49_chrXI 3841735 3843470 + ID = TGME49_313970; 1374 length = 1735 TGME49_chrVIIb 3286431 3288841 − ID = TGME49_258650; 1375 length = 2410 TGME49_chrIX 2706389 2708077 − ID = TGME49_288710; 1376 length = 1688 TGME49_chrX 912881 916723 − ID = TGME49_227570; 1377 length = 3842 TGME49_chrVIIb 1762209 1764225 + ID = TGME49_261410; 1378 length = 2016 TGME49_chrXI 2723240 2725414 + ID = TGME49_312490; 1379 length = 2174 TGME49_chrIX 932063 933944 − ID = TGME49_266840; 1380 length = 1881 TGME49_chrIa 296552 299464 + ID = TGME49_293390; 1381 length = 2912 TGME49_chrVI 3125605 3127814 − ID = TGME49_244210; 1382 length = 2209 TGME49_chrVIII 2067930 2069608 − ID = TGME49_232380; 1383 length = 1678 TGME49_chrXI 656827 661285 + ID = TGME49_309390; 1384 length = 4458 TGME49_chrXII 1846841 1847991 − ID = TGME49_217450; 1385 length = 1150 TGME49_chrVIIb 863548 865419 + ID = TGME49_263000; 1386 length = 1871 TGME49_chrXI 900050 902305 + ID = TGME49_309920; 1387 length = 2255 TGME49_chrVIIb 523777 525912 + ID = TGME49_263490; 1388 length = 2135 TGME49_chrIV 452586 457475 − ID = TGME49_320170; 1389 length = 4889 TGME49_chrIX 4345155 4348378 − ID = TGME49_291690; 1390 length = 3223 TGME49_chrX 5735321 5736518 + ID = TGME49_237140; 1391 length = 1197 TGME49_chrV 971313 973576 − ID = TGME49_213380; 1392 length = 2263 TGME49_chrX 3668011 3669970 + ID = TGME49_223660; 1393 length = 1959 TGME49_chrVIII 2956529 2961446 − ID = TGME49_274170; 1394 length = 4917 TGME49_chrIb 714291 719214 + ID = TGME49_208470; 1395 length = 4923 TGME49_chrXII 4009400 4010849 + ID = TGME49_248580; 1396 length = 1449 TGME49_chrV 2549712 2552335 − ID = TGME49_285190; 1397 length = 2623 TGME49_chrII 1927281 1928097 + ID = TGME49_297700; 1398 length = 816 TGME49_chrVIII 2689521 2690407 − ID = TGME49_233510; 1399 length = 886 TGME49_chrVIIa 2220731 2225084 + ID = TGME49_203800; 1400 length = 4353 TGME49_chrVI 2798189 2801702 + ID = TGME49_243700; 1401 length = 3513 TGME49_chrXI 810675 812617 + ID = TGME49_309790; 1402 length = 1942 TGME49_chrIa 521377 525024 + ID = TGME49_293720; 1403 length = 3647 TGME49_chrXII 4275825 4279900 + ID = TGME49_248970; 1404 length = 4075 TGME49_chrII 748920 750747 − ID = TGME49_222000; 1405 length = 1827 TGME49_chrIX 4400803 4404708 + ID = TGME49_291920; 1406 length = 3905 TGME49_chrVIII 5507253 5511071 − ID = TGME49_269950; 1407 length = 3818 TGME49_chrXII 1398435 1401335 − ID = TGME49_218590; 1408 length = 2900 TGME49_chrVIIb 1154398 1159024 + ID = TGME49_262568; 1409 length = 4626 TGME49_chrVIIb 2834684 2838145 − ID = TGME49_259260; 1410 length = 3461 TGME49_chrVIIb 1020393 1022780 − ID = TGME49_262800; 1411 length = 2387 TGME49_chrX 871374 874994 − ID = TGME49_227620; 1412 length = 3620 TGME49_chrIa 270952 273178 + ID = TGME49_293350; 1413 length = 2226 TGME49_chrXI 4579521 4583971 − ID = TGME49_315210; 1414 length = 4450 TGME49_chrX 2114737 2118243 − ID = TGME49_225710; 1415 length = 3506 TGME49_chrXI 915530 919805 − ID = TGME49_309930; 1416 length = 4275 TGME49_chrVIII 4874658 4879348 − ID = TGME49_270925; 1417 length = 4690 TGME49_chrVIIb 2396904 2397972 − ID = TGME49_260280; 1418 length = 1068 TGME49_chrVIII 4339933 4342675 − ID = TGME49_271840; 1419 length = 2742 TGME49_chrII 1978826 1981903 + ID = TGME49_297760; 1420 length = 3077 TGME49_chrVI 724098 726949 + ID = TGME49_239510; 1421 length = 2851 TGME49_chrVIII 394955 397268 − ID = TGME49_229710; 1422 length = 2313 TGME49_chrX 2538346 2540172 + ID = TGME49_225080; 1423 length = 1826 TGME49_chrX 3957033 3959160 − ID = TGME49_212260; 1424 length = 2127 TGME49_chrVIII 6036204 6038366 − ID = TGME49_269160; 1425 length = 2162 TGME49_chrIa 1507041 1511154 + ID = TGME49_295770; 1426 length = 4113 TGME49_chrVIIa 256069 257838 − ID = TGME49_280660; 1427 length = 1769 TGME49_chrXII 876562 878297 − ID = TGME49_219540; 1428 length = 1735 TGME49_chrVIIa 4386321 4390549 − ID = TGME49_282100; 1429 length = 4228 TGME49_chrX 7344432 7346618 + ID = TGME49_207040; 1430 length = 2186 TGME49_chrVIII 4560505 4562544 + ID = TGME49_271335; 1431 length = 2039 TGME49_chrXI 4316863 4319362 + ID = TGME49_314830; 1432 length = 2499 TGME49_chrVIIb 1422808 1424669 − ID = TGME49_262030; 1433 length = 1861 TGME49_chrVIII 2285212 2287451 − ID = TGME49_232830; 1434 length = 2239 TGME49_chrVIIa 3992533 3996332 − ID = TGME49_201170; 1435 length = 3799 TGME49_chrXI 1004000 1006816 + ID = TGME49_310010; 1436 length = 2816 TGME49_chrIX 5957299 5959752 − ID = TGME49_306310; 1437 length = 2453 TGME49_chrX 7344432 7345679 + ID = TGME49_207030; 1438 length = 1247 TGME49_chrVIIb 4253602 4256192 + ID = TGME49_257050; 1439 length = 2590 TGME49_chrX 1452312 1454768 − ID = TGME49_226670; 1440 length = 2456 TGME49_chrV 469797 472077 − ID = TGME49_220570; 1441 length = 2280 TGME49_chrIX 2094408 2096713 + ID = TGME49_264710; 1442 length = 2305 TGME49_chrVIIa 3662602 3666008 + ID = TGME49_202060; 1443 length = 3406 TGME49_chrXII 3253841 3255658 − ID = TGME49_247320; 1444 length = 1817 TGME49_chrIb 547531 550624 − ID = TGME49_208040; 1445 length = 3093 TGME49_chrIX 2133128 2135664 + ID = TGME49_264660; 1446 length = 2536 TGME49_chrIX 1292458 1295329 − ID = TGME49_266120; 1447 length = 2871 TGME49_chrXI 1328980 1332607 + ID = TGME49_310430; 1448 length = 3627 TGME49_chrX 6270785 6272853 − ID = TGME49_214370; 1449 length = 2068 TGME49_chrVIIb 251585 254066 − ID = TGME49_264000; 1450 length = 2481 TGME49_chrVI 1612726 1614168 + ID = TGME49_240990; 1451 length = 1442 TGME49_chrIX 1530142 1532118 − ID = TGME49_265500; 1452 length = 1976 TGME49_chrIX 6232749 6234329 − ID = TGME49_306630; 1453 length = 1580 TGME49_chrXI 4753701 4755221 + ID = TGME49_315495; 1454 length = 1520 TGME49_chrVIIa 3844338 3846794 − ID = TGME49_201700; 1455 length = 2456 TGME49_chrXII 1058438 1061957 − ID = TGME49_219222; 1456 length = 3519 TGME49_chrVIII 3632654 3634741 + ID = TGME49_273140; 1457 length = 2087 TGME49_chrVIII 5032871 5035049 − ID = TGME49_270740; 1458 length = 2178 TGME49_chrIa 89272 92865 + ID = TGME49_293010; 1459 length = 3593 TGME49_chrXII 2686419 2690798 − ID = TGME49_246140; 1460 length = 4379 TGME49_chrXII 2197081 2200494 + ID = TGME49_217880; 1461 length = 3413 TGME49_chrXI 4536782 4540443 + ID = TGME49_315165; 1462 length = 3661 TGME49_chrXII 727484 728939 − ID = TGME49_219690; 1463 length = 1455 TGME49_chrVIIb 4699937 4702102 + ID = TGME49_255715; 1464 length = 2165 TGME49_chrVIIb 4573700 4576785 + ID = TGME49_255980; 1465 length = 3085 TGME49_chrVIIb 475047 477267 − ID = TGME49_263570; 1466 length = 2220 TGME49_chrV 1705802 1710404 + ID = TGME49_286720; 1467 length = 4602 TGME49_chrV 2326677 2329241 − ID = TGME49_285650; 1468 length = 2564 TGME49_chrIb 1641650 1645144 + ID = TGME49_321660; 1469 length = 3494 TGME49_chrVIII 2198843 2203273 + ID = TGME49_232640; 1470 length = 4430 TGME49_chrV 1532883 1536115 + ID = TGME49_287180; 1471 length = 3232 TGME49_chrV 1908950 1912837 − ID = TGME49_286230; 1472 length = 3887 TGME49_chrXII 4413457 4417115 + ID = TGME49_249270; 1473 length = 3658 TGME49_chrIX 5898832 5900782 − ID = TGME49_306250; 1474 length = 1950 TGME49_chrVIIb 4154765 4156893 − ID = TGME49_257290; 1475 length = 2128 TGME49_chrVIII 1268914 1270935 + ID = TGME49_231150; 1476 length = 2021 TGME49_chrVIIb 971154 973119 − ID = TGME49_262870; 1477 length = 1965 TGME49_chrIV 282678 285486 + ID = TGME49_320515; 1478 length = 2808 TGME49_chrXII 6880772 6883692 + ID = TGME49_276880; 1479 length = 2920 TGME49_chrX 6032756 6036014 + ID = TGME49_214110; 1480 length = 3258 TGME49_chrX 4061115 4063643 + ID = TGME49_212100; 1481 length = 2528 TGME49_chrV 2498999 2501500 − ID = TGME49_285240; 1482 length = 2501 TGME49_chrXII 1724144 1728800 − ID = TGME49_218188; 1483 length = 4656 TGME49_chrIX 5437186 5438779 − ID = TGME49_305485; 1484 length = 1593 TGME49_chrVIII 6795589 6797461 − ID = TGME49_200310; 1485 length = 1872 TGME49_chrIX 1829415 1830688 − ID = TGME49_265030; 1486 length = 1273 TGME49_chrVI 1828265 1830308 + ID = TGME49_242020; 1487 length = 2043 TGME49_chrVIII 2016463 2018840 − ID = TGME49_232320; 1488 length = 2377 TGME49_chrXI 3740855 3743951 − ID = TGME49_313852; 1489 length = 3096 TGME49_chrVIIb 4275109 4277123 − ID = TGME49_257030; 1490 length = 2014 TGME49_chrX 6767981 6769751 − ID = TGME49_215120; 1491 length = 1770 TGME49_chrVIIa 2075756 2076930 + ID = TGME49_203970; 1492 length = 1174 TGME49_chrVIIb 2416856 2418383 − ID = TGME49_260260; 1493 length = 1527 TGME49_chrIX 3779931 3784973 + ID = TGME49_290630; 1494 length = 5042 TGME49_chrVIIb 581365 584740 + ID = TGME49_263390; 1495 length = 3375 TGME49_chrXII 4466466 4468532 − ID = TGME49_249330; 1496 length = 2066 TGME49_chrII 1858989 1860788 + ID = TGME49_297530; 1497 length = 1799 TGME49_chrII 22256 25319 − ID = TGME49_220840; 1498 length = 3063 TGME49_chrIX 3868643 3870136 + ID = TGME49_290730; 1499 length = 1493 TGME49_chrXI 551152 554422 + ID = TGME49_309200; 1500 length = 3270 TGME49_chrIb 1422277 1424478 − ID = TGME49_209730; 1501 length = 2201 TGME49_chrIX 1830908 1832938 + ID = TGME49_265020; 1502 length = 2030 TGME49_chrXII 2839463 2841372 − ID = TGME49_246535; 1503 length = 1909 TGME49_chrVIII 5830510 5832051 − ID = TGME49_269413; 1504 length = 1541 TGME49_chrVIIb 3160690 3162547 + ID = TGME49_258826; 1505 length = 1857 TGME49_chrXI 4307313 4309840 + ID = TGME49_314810; 1506 length = 2527 TGME49_chrVIII 406789 409738 − ID = TGME49_229730; 1507 length = 2949 TGME49_chrXII 2456140 2459097 + ID = TGME49_245670; 1508 length = 2957 TGME49_chrVIIa 2619487 2621645 − ID = TGME49_203290; 1509 length = 2158 TGME49_chrV 1924282 1927117 + ID = TGME49_286190; 1510 length = 2835 TGME49_chrVI 716743 721319 + ID = TGME49_239500; 1511 length = 4576 TGME49_chrX 5770090 5772025 − ID = TGME49_237180; 1512 length = 1935 TGME49_chrXII 2832970 2834932 − ID = TGME49_246520; 1513 length = 1962 TGME49_chrXII 5499795 5502016 − ID = TGME49_251620; 1514 length = 2221 TGME49_chrVIII 3996074 3999088 + ID = TGME49_272400; 1515 length = 3014 TGME49_chrIX 1961567 1963588 − ID = TGME49_264860; 1516 length = 2021 TGME49_chrVIIa 1028393 1032556 + ID = TGME49_206380; 1517 length = 4163 TGME49_chrX 3004741 3008120 − ID = TGME49_224530; 1518 length = 3379 TGME49_chrII 1710951 1714500 − ID = TGME49_297350; 1519 length = 3549 TGME49_chrV 244391 246292 + ID = TGME49_220260; 1520 length = 1901 TGME49_chrX 4446902 4449402 − ID = TGME49_234540; 1521 length = 2500 TGME49_chrVIII 3410793 3412947 + ID = TGME49_273540; 1522 length = 2154 TGME49_chrXI 3686190 3687061 + ID = TGME49_313775; 1523 length = 871 TGME49_chrIV 1961999 1964761 − ID = TGME49_211030; 1524 length = 2762 TGME49_chrVIIb 4217527 4220783 + ID = TGME49_257100; 1525 length = 3256 TGME49_chrIV 2355261 2356404 − ID = TGME49_301260; 1526 length = 1143 TGME49_chrVIIb 1978655 1980752 + ID = TGME49_261000; 1527 length = 2097 TGME49_chrXII 1707434 1711430 − ID = TGME49_218195; 1528 length = 3996 TGME49_chrVI 2626707 2630269 − ID = TGME49_243430; 1529 length = 3562 TGME49_chrVIIb 3086523 3088120 − ID = TGME49_258930; 1530 length = 1597 TGME49_chrIb 820471 822527 − ID = TGME49_208710; 1531 length = 2056 TGME49_chrX 6097197 6099437 − ID = TGME49_214190; 1532 length = 2240 TGME49_chrX 5747724 5750210 − ID = TGME49_237150; 1533 length = 2486 TGME49_chrIb 1052146 1053746 + ID = TGME49_209120; 1534 length = 1600 TGME49_chrVIIb 821098 823077 + ID = TGME49_263080; 1535 length = 1979 TGME49_chrXII 1276521 1280802 − ID = TGME49_218830; 1536 length = 4281 TGME49_chrXII 1314254 1315857 − ID = TGME49_218780; 1537 length = 1603 TGME49_chrVIII 3808316 3811592 + ID = TGME49_272660; 1538 length = 3276 TGME49_chrXII 3339927 3343970 − ID = TGME49_247440; 1539 length = 4043 TGME49_chrX 669041 669809 − ID = TGME49_228020; 1540 length = 768 TGME49_chrIa 1801426 1803846 − ID = TGME49_295380; 1541 length = 2420 TGME49_chrIX 1152435 1155997 + ID = TGME49_266400; 1542 length = 3562 TGME49_chrXII 4736176 4738097 − ID = TGME49_249685; 1543 length = 1921 TGME49_chrVIII 6462646 6464783 − ID = TGME49_268400; 1544 length = 2137 TGME49_chrX 2405925 2408633 + ID = TGME49_225200; 1545 length = 2708 TGME49_chrX 4250667 4254283 + ID = TGME49_234270; 1546 length = 3616 TGME49_chrIV 2580676 2583197 − ID = TGME49_237835; 1547 length = 2521 TGME49_chrX 2837717 2842141 − ID = TGME49_224760; 1548 length = 4424 TGME49_chrVIIa 1225490 1228154 + ID = TGME49_205658; 1549 length = 2664 TGME49_chrIV 472782 476325 − ID = TGME49_320150; 1550 length = 3543 TGME49_chrVIII 2495326 2497228 − ID = TGME49_233200; 1551 length = 1902 TGME49_chrIX 1398246 1400896 − ID = TGME49_265870; 1552 length = 2650 TGME49_chrVIIb 779047 782310 − ID = TGME49_263135; 1553 length = 3263 TGME49_chrVIIa 2499387 2501343 + ID = TGME49_203440; 1554 length = 1956 TGME49_chrXII 3179343 3181561 + ID = TGME49_247230; 1555 length = 2218 TGME49_chrVIIb 906498 907438 + ID = TGME49_262940; 1556 length = 940 TGME49_chrX 3106086 3109088 + ID = TGME49_224290; 1557 length = 3002 TGME49_chrVIIb 2972536 2974185 − ID = TGME49_259100; 1558 length = 1649 TGME49_chrVIII 322273 327193 − ID = TGME49_229620; 1559 length = 4920 TGME49_chrVI 2726419 2728299 − ID = TGME49_243570; 1560 length = 1880 TGME49_chrIb 1763476 1764810 − ID = TGME49_321510; 1561 length = 1334 TGME49_chrVIII 1915936 1917426 − ID = TGME49_232170; 1562 length = 1490 TGME49_chrXI 1198381 1203275 − ID = TGME49_310260; 1563 length = 4894 TGME49_chrV 1164970 1166774 − ID = TGME49_213600; 1564 length = 1804 TGME49_chrXII 1120459 1123972 − ID = TGME49_219125; 1565 length = 3513 TGME49_chrXI 3087960 3092164 − ID = TGME49_313080; 1566 length = 4204 TGME49_chrXI 1976585 1979964 + ID = TGME49_311335; 1567 length = 3379 TGME49_chrXII 5059554 5061900 − ID = TGME49_250340; 1568 length = 2346 TGME49_chrIX 708789 710487 + ID = TGME49_267330; 1569 length = 1698 TGME49_chrVI 2874483 2878854 + ID = TGME49_243910; 1570 length = 4371 TGME49_chrX 3857496 3859431 − ID = TGME49_223420; 1571 length = 1935 TGME49_chrVIIa 176036 178132 + ID = TGME49_280690; 1572 length = 2096 TGME49_chrX 5637919 5640447 + ID = TGME49_236980; 1573 length = 2528 TGME49_chrVIII 5981273 5982851 − ID = TGME49_269225; 1574 length = 1578 TGME49_chrIV 1821118 1825235 + ID = TGME49_211330; 1575 length = 4117 TGME49_chrV 2548699 2551643 + ID = TGME49_285180; 1576 length = 2944 TGME49_chrVIIb 1989290 1990938 + ID = TGME49_260990; 1577 length = 1648 TGME49_chrX 1834669 1836342 + ID = TGME49_226060; 1578 length = 1673 TGME49_chrV 817024 819593 + ID = TGME49_213050; 1579 length = 2569 TGME49_chrVIII 2234318 2235909 + ID = TGME49_232710; 1580 length = 1591 TGME49_chrVIIb 3147875 3150412 + ID = TGME49_258832; 1581 length = 2537 TGME49_chrVIIb 4740043 4742016 − ID = TGME49_255680; 1582 length = 1973 TGME49_chrVIII 3585349 3587718 − ID = TGME49_273340; 1583 length = 2369 TGME49_chrVI 1619493 1622431 − ID = TGME49_241000; 1584 length = 2938 TGME49_chrVI 3235482 3240036 + ID = TGME49_244400; 1585 length = 4554 TGME49_chrVIII 4624312 4626375 − ID = TGME49_271250; 1586 length = 2063 TGME49_chrIV 1260400 1264074 − ID = TGME49_318525; 1587 length = 3674 TGME49_chrXII 2946217 2948125 + ID = TGME49_246730; 1588 length = 1908 TGME49_chrV 1102556 1104367 + ID = TGME49_213490; 1589 length = 1811 TGME49_chrVIIb 1064528 1067088 − ID = TGME49_262715; 1590 length = 2560 TGME49_chrIV 564447 565815 − ID = TGME49_320040; 1591 length = 1368 TGME49_chrV 1295918 1298121 − ID = TGME49_213760; 1592 length = 2203 TGME49_chrVIII 1859181 1860943 − ID = TGME49_232100; 1593 length = 1762 TGME49_chrXI 5852137 5854406 + ID = TGME49_216840; 1594 length = 2269 TGME49_chrX 6047181 6050358 + ID = TGME49_214130; 1595 length = 3177 TGME49_chrV 702364 705795 + ID = TGME49_212937; 1596 length = 3431 TGME49_chrX 644166 645619 − ID = TGME49_228065; 1597 length = 1453 TGME49_chrIb 707596 710331 + ID = TGME49_208440; 1598 length = 2735 TGME49_chrVIII 4254025 4256840 + ID = TGME49_271970; 1599 length = 2815 TGME49_chrVIIa 1752677 1754734 − ID = TGME49_204490; 1600 length = 2057 TGME49_chrIX 3031260 3032617 + ID = TGME49_289160; 1601 length = 1357 TGME49_chrIa 1610589 1612536 − ID = TGME49_295690; 1602 length = 1947 TGME49_chrXII 3652284 3655006 + ID = TGME49_248100; 1603 length = 2722 TGME49_chrV 2253285 2254950 − ID = TGME49_285760; 1604 length = 1665 TGME49_chrIa 644712 646745 − ID = TGME49_294010; 1605 length = 2033 TGME49_chrVIIb 2634842 2637275 − ID = TGME49_259890; 1606 length = 2433 TGME49_chrXII 3357594 3360110 − ID = TGME49_247460; 1607 length = 2516 TGME49_chrIb 458487 461835 − ID = TGME49_207950; 1608 length = 3348 TGME49_chrII 309176 312120 − ID = TGME49_221390; 1609 length = 2944 TGME49_chrXII 5240975 5243070 − ID = TGME49_250810; 1610 length = 2095 TGME49_chrIX 1501064 1504713 − ID = TGME49_265530; 1611 length = 3649 TGME49_chrIb 48324 49906 − ID = TGME49_207420; 1612 length = 1582 TGME49_chrVIIa 2960709 2963102 + ID = TGME49_202880; 1613 length = 2393 TGME49_chrXII 2759303 2762582 − ID = TGME49_246230; 1614 length = 3279 TGME49_chrVIIa 3364291 3368281 + ID = TGME49_202380; 1615 length = 3990 TGME49_chrVIII 5847471 5851413 + ID = TGME49_269380; 1616 length = 3942 TGME49_chrXI 2803915 2808538 + ID = TGME49_312590; 1617 length = 4623 TGME49_chrXI 3587275 3589602 + ID = TGME49_313665; 1618 length = 2327 TGME49_chrXII 4168320 4169758 + ID = TGME49_248780; 1619 length = 1438 TGME49_chrX 5074453 5075975 + ID = TGME49_235720; 1620 length = 1522 TGME49_chrII 2127562 2129984 + ID = TGME49_297950; 1621 length = 2422 TGME49_chrVIIb 894167 897847 − ID = TGME49_262970; 1622 length = 3680 TGME49_chrVIII 2420778 2422638 + ID = TGME49_233110; 1623 length = 1860 TGME49_chrXII 5430634 5433016 − ID = TGME49_251490; 1624 length = 2382 TGME49_chrX 438371 442269 + ID = TGME49_228280; 1625 length = 3898 TGME49_chrV 2053342 2058060 − ID = TGME49_286020; 1626 length = 4718 TGME49_chrIX 1548370 1553308 − ID = TGME49_265450; 1627 length = 4938 TGME49_chrIb 1361665 1366149 − ID = TGME49_209610; 1628 length = 4484 TGME49_chrII 1160506 1162386 − ID = TGME49_222440; 1629 length = 1880 TGME49_chrXII 3825625 3827372 + ID = TGME49_248370; 1630 length = 1747 TGME49_chrIa 695084 698240 + ID = TGME49_294200; 1631 length = 3156 TGME49_chrXI 6391216 6392903 − ID = TGME49_216130; 1632 length = 1687 TGME49_chrXI 496472 497645 + ID = TGME49_309095; 1633 length = 1173 TGME49_chrVI 2105036 2106954 − ID = TGME49_242610; 1634 length = 1918 TGME49_chrVIIa 20277 22070 − ID = TGME49_279550; 1635 length = 1793 TGME49_chrVIII 5588163 5591148 + ID = TGME49_269810; 1636 length = 2985 TGME49_chrII 1643776 1646520 − ID = TGME49_297245; 1637 length = 2744 TGME49_chrXII 1661314 1663812 − ID = TGME49_218230; 1638 length = 2498 TGME49_chrVIIa 1958747 1961164 − ID = TGME49_204140; 1639 length = 2417 TGME49_chrIV 1317765 1320416 + ID = TGME49_318450; 1640 length = 2651 TGME49_chrX 4551871 4556156 − ID = TGME49_234930; 1641 length = 4285 TGME49_chrV 1361167 1363437 − ID = TGME49_213830; 1642 length = 2270 TGME49_chrV 2135398 2138100 − ID = TGME49_285940; 1643 length = 2702 TGME49_chrVIII 4288270 4290925 + ID = TGME49_271910; 1644 length = 2655 TGME49_chrX 5448896 5450860 + ID = TGME49_236620; 1645 length = 1964 TGME49_chrX 7170482 7175111 − ID = TGME49_275310; 1646 length = 4629 TGME49_chrIX 3092344 3096555 − ID = TGME49_289218; 1647 length = 4211 TGME49_chrIV 866827 869130 + ID = TGME49_319590; 1648 length = 2303 TGME49_chrX 6109656 6111516 − ID = TGME49_214200; 1649 length = 1860 TGME49_chrIa 716367 719854 − ID = TGME49_294210; 1650 length = 3487 TGME49_chrIX 2520742 2523456 − ID = TGME49_288420; 1651 length = 2714 TGME49_chrIX 3369880 3371358 − ID = TGME49_289660; 1652 length = 1478 TGME49_chrX 456771 458903 + ID = TGME49_228240; 1653 length = 2132 TGME49_chrVIIb 2969500 2972803 + ID = TGME49_259090; 1654 length = 3303 TGME49_chrVIIb 711535 716415 − ID = TGME49_263210; 1655 length = 4880 TGME49_chrVIII 2122538 2126263 − ID = TGME49_232500; 1656 length = 3725 TGME49_chrIV 2096934 2099104 − ID = TGME49_210750; 1657 length = 2170 TGME49_chrIb 863212 866544 + ID = TGME49_208800; 1658 length = 3332 TGME49_chrVIII 5219785 5222055 − ID = TGME49_270520; 1659 length = 2270 TGME49_chrVI 1285261 1288152 − ID = TGME49_240450; 1660 length = 2891 TGME49_chrVIIa 3031763 3033039 − ID = TGME49_202790; 1661 length = 1276 TGME49_chrXI 3235407 3237049 − ID = TGME49_313277; 1662 length = 1642 TGME49_chrXII 4460349 4461980 − ID = TGME49_249325; 1663 length = 1631 TGME49_chrVIIb 1062098 1065932 + ID = TGME49_262710; 1664 length = 3834 TGME49_chrVIII 2155428 2158102 + ID = TGME49_232550; 1665 length = 2674 TGME49_chrIX 325672 328132 + ID = TGME49_267820; 1666 length = 2460 TGME49_chrXI 5157299 5158701 + ID = TGME49_316150; 1667 length = 1402 TGME49_chrVIIb 4842347 4847324 + ID = TGME49_255400; 1668 length = 4977 TGME49_chrX 2287678 2289457 − ID = TGME49_225360; 1669 length = 1779 TGME49_chrVIIa 3819058 3822835 + ID = TGME49_201750; 1670 length = 3777 TGME49_chrX 4843932 4845765 − ID = TGME49_235398; 1671 length = 1833 TGME49_chrIV 1145000 1147010 + ID = TGME49_318690; 1672 length = 2010 TGME49_chrXII 5588646 5590856 − ID = TGME49_251780; 1673 length = 2210 TGME49_chrXI 6129114 6134065 − ID = TGME49_216470; 1674 length = 4951 TGME49_chrVI 455338 457067 − ID = TGME49_239083; 1675 length = 1729 TGME49_chrVIII 3289883 3294737 + ID = TGME49_273750; 1676 length = 4854 TGME49_chrVIII 3689219 3691099 + ID = TGME49_273060; 1677 length = 1880 TGME49_chrX 3326589 3328196 − ID = TGME49_224100; 1678 length = 1607 TGME49_chrVIIa 1060833 1063141 + ID = TGME49_206320; 1679 length = 2308 TGME49_chrII 1301776 1305290 + ID = TGME49_222910; 1680 length = 3514 TGME49_chrII 1512263 1514584 + ID = TGME49_297065; 1681 length = 2321 TGME49_chrVIII 3030733 3033855 + ID = TGME49_274090; 1682 length = 3122 TGME49_chrII 342210 344003 + ID = TGME49_221430; 1683 length = 1793 TGME49_chrVI 1320689 1322846 − ID = TGME49_240560; 1684 length = 2157 TGME49_chrXI 4851796 4855798 + ID = TGME49_315610; 1685 length = 4002 TGME49_chrXII 2866217 2868700 + ID = TGME49_246590; 1686 length = 2483 TGME49_chrVIIb 2395067 2397478 + ID = TGME49_260270; 1687 length = 2411 TGME49_chrV 766839 769527 + ID = TGME49_213000; 1688 length = 2688 TGME49_chrXII 1927136 1929197 − ID = TGME49_217580; 1689 length = 2061 TGME49_chrXII 6597836 6600162 − ID = TGME49_275568; 1690 length = 2326 TGME49_chrIX 5330740 5332155 + ID = TGME49_305280; 1691 length = 1415 TGME49_chrX 6259145 6260711 + ID = TGME49_214350; 1692 length = 1566 TGME49_chrIX 2730243 2732515 − ID = TGME49_288765; 1693 length = 2272 TGME49_chrXI 4169227 4173719 − ID = TGME49_314515; 1694 length = 4492 TGME49_chrXI 1722895 1726565 + ID = TGME49_311020; 1695 length = 3670 TGME49_chrXI 2059780 2062470 + ID = TGME49_311410; 1696 length = 2690 TGME49_chrVIIa 4202011 4206408 + ID = TGME49_281580; 1697 length = 4397 TGME49_chrVIIa 2946359 2950755 + ID = TGME49_202900; 1698 length = 4396 TGME49_chrVIIb 2678088 2682997 + ID = TGME49_259830; 1699 length = 4909 TGME49_chrVIIa 899877 903405 + ID = TGME49_206510; 1700 length = 3528 TGME49_chrXI 3996077 3999430 − ID = TGME49_314310; 1701 length = 3353 TGME49_chrXII 5353411 5355727 + ID = TGME49_251400; 1702 length = 2316 TGME49_chrXII 2176868 2180818 + ID = TGME49_217860; 1703 length = 3950 TGME49_chrVIII 5792673 5796876 − ID = TGME49_269450; 1704 length = 4203 TGME49_chrVIII 6863500 6867930 − ID = TGME49_200400; 1705 length = 4430 TGME49_chrIX 1642011 1646868 − ID = TGME49_265270; 1706 length = 4857 TGME49_chrIa 451232 453213 + ID = TGME49_293610; 1707 length = 1981 TGME49_chrVI 1445741 1449188 + ID = TGME49_240800; 1708 length = 3447 TGME49_chrVIIb 899808 902193 + ID = TGME49_262950; 1709 length = 2385 TGME49_chrXII 5526551 5531499 + ID = TGME49_251690; 1710 length = 4948 TGME49_chrIV 2154878 2157331 + ID = TGME49_210690; 1711 length = 2453 TGME49_chrVIIa 2244701 2247997 + ID = TGME49_203770; 1712 length = 3296 TGME49_chrVIIb 1773969 1777524 − ID = TGME49_261400; 1713 length = 3555 TGME49_chrIX 2087644 2089518 − ID = TGME49_264730; 1714 length = 1874 TGME49_chrX 5326096 5328125 − ID = TGME49_236200; 1715 length = 2029 TGME49_chrIX 5280180 5282539 + ID = TGME49_305200; 1716 length = 2359 TGME49_chrV 1815047 1818388 + ID = TGME49_286480; 1717 length = 3341 TGME49_chrVIIa 624310 629301 + ID = TGME49_304700; 1718 length = 4991 TGME49_chrII 505138 509495 − ID = TGME49_221630; 1719 length = 4357 TGME49_chrVI 3153014 3156401 + ID = TGME49_244280; 1720 length = 3387 TGME49_chrVIII 3997097 3999384 − ID = TGME49_272410; 1721 length = 2287 TGME49_chrXII 6205376 6207991 + ID = TGME49_278245; 1722 length = 2615 TGME49_chrVIII 5108236 5110579 − ID = TGME49_270650; 1723 length = 2343 TGME49_chrIX 1415881 1418195 + ID = TGME49_265840; 1724 length = 2314 TGME49_chrVIIb 3863097 3864612 − ID = TGME49_257740; 1725 length = 1515 TGME49_chrVIII 4215825 4218765 − ID = TGME49_272020; 1726 length = 2940 TGME49_chrVIIa 1629342 1632196 − ID = TGME49_205120; 1727 length = 2854 TGME49_chrVIIa 463960 467129 + ID = TGME49_280390; 1728 length = 3169 TGME49_chrVIIa 1426542 1431194 − ID = TGME49_205390; 1729 length = 4652 TGME49_chrII 201437 204275 − ID = TGME49_221275; 1730 length = 2838 TGME49_chrXII 2437627 2439102 − ID = TGME49_245620; 1731 length = 1475 TGME49_chrVIIb 2332162 2334662 − ID = TGME49_260370; 1732 length = 2500 TGME49_chrVIIa 788333 792905 + ID = TGME49_206600; 1733 length = 4572 TGME49_chrIX 4108788 4113576 + ID = TGME49_291090; 1734 length = 4788 TGME49_chrIX 4682427 4683833 + ID = TGME49_292325; 1735 length = 1406 TGME49_chrXI 2417445 2418466 − ID = TGME49_312075; 1736 length = 1021 TGME49_chrIa 556012 560537 + ID = TGME49_293790; 1737 length = 4525 TGME49_chrIX 779646 784608 + ID = TGME49_267090; 1738 length = 4962 TGME49_chrX 2592957 2594193 + ID = TGME49_225005; 1739 length = 1236 TGME49_chrIX 2410595 2414911 − ID = TGME49_288245; 1740 length = 4316 TGME49_chrVIIb 2602303 2605077 + ID = TGME49_259940; 1741 length = 2774 TGME49_chrX 5395871 5397679 + ID = TGME49_236520; 1742 length = 1808 TGME49_chrIV 1107275 1109514 + ID = TGME49_318750; 1743 length = 2239 TGME49_chrVI 191582 194227 + ID = TGME49_238400; 1744 length = 2645 TGME49_chrX 6586789 6588930 + ID = TGME49_214920; 1745 length = 2141 TGME49_chrXII 6371094 6373426 − ID = TGME49_277990; 1746 length = 2332 TGME49_chrIa 1812506 1814521 − ID = TGME49_295350; 1747 length = 2015 TGME49_chrXII 6656982 6660694 + ID = TGME49_277500; 1748 length = 3712 TGME49_chrXII 2663643 2665815 + ID = TGME49_246100; 1749 length = 2172 TGME49_chrXI 436997 438672 − ID = TGME49_309010; 1750 length = 1675 TGME49_chrIX 5442829 5445816 − ID = TGME49_305498; 1751 length = 2987 TGME49_chrVI 41637 43605 + ID = TGME49_238060; 1752 length = 1968 TGME49_chrXII 613045 617971 + ID = TGME49_219828; 1753 length = 4926 TGME49_chrX 2026020 2028673 − ID = TGME49_225820; 1754 length = 2653 TGME49_chrIX 3690964 3692526 + ID = TGME49_290300; 1755 length = 1562 TGME49_chrIX 652699 654379 + ID = TGME49_267435; 1756 length = 1680 TGME49_chrV 489825 492876 − ID = TGME49_220610; 1757 length = 3051 TGME49_chrVIIb 486067 488472 + ID = TGME49_263540; 1758 length = 2405 TGME49_chrVIII 3283733 3286012 + ID = TGME49_273770; 1759 length = 2279 TGME49_chrIb 978776 983209 + ID = TGME49_209010; 1760 length = 4433 TGME49_chrVI 1775119 1776850 − ID = TGME49_241860; 1761 length = 1731 TGME49_chrIa 1146951 1148726 − ID = TGME49_294790; 1762 length = 1775 TGME49_chrXII 1041731 1043438 − ID = TGME49_219250; 1763 length = 1707 TGME49_chrVIII 733619 737486 − ID = TGME49_230350; 1764 length = 3867 TGME49_chrII 1603694 1605698 − ID = TGME49_297190; 1765 length = 2004 TGME49_chrIX 2711191 2713335 − ID = TGME49_288720; 1766 length = 2144 TGME49_chrX 1196543 1199550 + ID = TGME49_226950; 1767 length = 3007 TGME49_chrIX 5393544 5395750 + ID = TGME49_305455; 1768 length = 2206 TGME49_chrXI 1499161 1503181 + ID = TGME49_310660; 1769 length = 4020 TGME49_chrXI 5008254 5010201 + ID = TGME49_315820; 1770 length = 1947 TGME49_chrVI 1390368 1392791 − ID = TGME49_240690; 1771 length = 2423 TGME49_chrII 1120393 1123132 + ID = TGME49_222410; 1772 length = 2739 TGME49_chrX 739417 741694 − ID = TGME49_227920; 1773 length = 2277 TGME49_chrVIII 5548282 5553068 − ID = TGME49_269910; 1774 length = 4786 TGME49_chrVIII 503704 505886 − ID = TGME49_229990; 1775 length = 2182 TGME49_chrX 2521891 2524155 + ID = TGME49_225102; 1776 length = 2264 TGME49_chrVIIb 2469232 2470805 + ID = TGME49_260190; 1777 length = 1573 TGME49_chrIX 381279 384341 + ID = TGME49_267750; 1778 length = 3062 TGME49_chrXII 2603118 2605598 + ID = TGME49_246030; 1779 length = 2480 TGME49_chrII 1373856 1375582 + ID = TGME49_223025; 1780 length = 1726 TGME49_chrVIIb 2167761 2170472 − ID = TGME49_260550; 1781 length = 2711 TGME49_chrXI 4240194 4244498 − ID = TGME49_314710; 1782 length = 4304 TGME49_chrVIIa 293961 296113 − ID = TGME49_280570; 1783 length = 2152 TGME49_chrIX 1323487 1325964 − ID = TGME49_266065; 1784 length = 2477 TGME49_chrVIII 1513803 1516857 + ID = TGME49_231640; 1785 length = 3054 TGME49_chrV 342801 346665 + ID = TGME49_220390; 1786 length = 3864 TGME49_chrVIIa 1663101 1666170 + ID = TGME49_205030; 1787 length = 3069 TGME49_chrVI 2847971 2852954 − ID = TGME49_243760; 1788 length = 4983 TGME49_chrIX 5351150 5353348 + ID = TGME49_305320; 1789 length = 2198 TGME49_chrXII 4131891 4133450 − ID = TGME49_248730; 1790 length = 1559 TGME49_chrXI 133543 134623 + ID = TGME49_306990; 1791 length = 1080 TGME49_chrX 6353248 6354650 − ID = TGME49_214550; 1792 length = 1402 TGME49_chrVIII 6042411 6044655 + ID = TGME49_269140; 1793 length = 2244 TGME49_chrIX 1688833 1690933 − ID = TGME49_265230; 1794 length = 2100 TGME49_chrIa 306442 309887 + ID = TGME49_293420; 1795 length = 3445 TGME49_chrVIIa 1824928 1827582 + ID = TGME49_204390; 1796 length = 2654 TGME49_chrXII 951031 952710 + ID = TGME49_219430; 1797 length = 1679 TGME49_chrVI 581992 583744 − ID = TGME49_239350; 1798 length = 1752 TGME49_chrX 3441657 3444661 − ID = TGME49_223940; 1799 length = 3004 TGME49_chrVIII 846765 849139 + ID = TGME49_230520; 1800 length = 2374 TGME49_chrXII 3323790 3326774 + ID = TGME49_247400; 1801 length = 2984 TGME49_chrVIIa 2920724 2923694 − ID = TGME49_202960; 1802 length = 2970 TGME49_chrXI 4578541 4582751 + ID = TGME49_315220; 1803 length = 4210 TGME49_chrIX 1528778 1531783 + ID = TGME49_265470; 1804 length = 3005 TGME49_chrXI 1239947 1242270 − ID = TGME49_310290; 1805 length = 2323 TGME49_chrVIIb 222702 224691 − ID = TGME49_264040; 1806 length = 1989 TGME49_chrVIII 405193 409738 − ID = TGME49_229720; 1807 length = 4545 TGME49_chrVIIa 625071 629635 − ID = TGME49_304680; 1808 length = 4564 TGME49_chrIX 2507287 2509481 − ID = TGME49_288400; 1809 length = 2194 TGME49_chrVIIa 3260937 3263671 − ID = TGME49_202530; 1810 length = 2734 TGME49_chrIX 227007 229288 + ID = TGME49_279360; 1811 length = 2281 TGME49_chrX 4021655 4024338 + ID = TGME49_212140; 1812 length = 2683 TGME49_chrVIIb 1215908 1219966 + ID = TGME49_262460; 1813 length = 4058 TGME49_chrX 7457937 7460592 − ID = TGME49_207230; 1814 length = 2655 TGME49_chrVIII 1071514 1075639 − ID = TGME49_230870; 1815 length = 4125 TGME49_chrX 5029202 5030634 − ID = TGME49_235660; 1816 length = 1432 TGME49_chrVIIb 4838297 4840986 − ID = TGME49_255420; 1817 length = 2689 TGME49_chrVIII 574328 576120 − ID = TGME49_230070; 1818 length = 1792 TGME49_chrVIIa 1434529 1437210 + ID = TGME49_205370; 1819 length = 2681 TGME49_chrVIIb 3184714 3187955 − ID = TGME49_258790; 1820 length = 3241 TGME49_chrVIIb 452002 453575 + ID = TGME49_263595; 1821 length = 1573 TGME49_chrII 1799177 1801013 − ID = TGME49_297460; 1822 length = 1836 TGME49_chrIX 1348019 1350404 + ID = TGME49_266010; 1823 length = 2385 TGME49_chrXI 422982 426252 − ID = TGME49_308990; 1824 length = 3270 TGME49_chrVIIa 2638640 2643428 + ID = TGME49_203250; 1825 length = 4788 TGME49_chrXII 3112106 3117089 + ID = TGME49_247030; 1826 length = 4983 TGME49_chrV 1786117 1787739 + ID = TGME49_286550; 1827 length = 1622 TGME49_chrIb 1636369 1639495 − ID = TGME49_321690; 1828 length = 3126 TGME49_chrXII 4744062 4745703 − ID = TGME49_249698; 1829 length = 1641 TGME49_chrXI 1049288 1054295 − ID = TGME49_310080; 1830 length = 5007 TGME49_chrXII 2997364 3001613 + ID = TGME49_246800; 1831 length = 4249 TGME49_chrVIIa 276480 280573 − ID = TGME49_280600; 1832 length = 4093 TGME49_chrVIIa 2044834 2047221 − ID = TGME49_204040; 1833 length = 2387 TGME49_chrIV 1443575 1445262 − ID = TGME49_318290; 1834 length = 1687 TGME49_chrVIIb 1358543 1363574 − ID = TGME49_262125; 1835 length = 5031 TGME49_chrXII 1889739 1893641 − ID = TGME49_217520; 1836 length = 3902 TGME49_chrVIII 6218156 6222777 + ID = TGME49_268890; 1837 length = 4621 TGME49_chrIX 212823 215942 − ID = TGME49_279390; 1838 length = 3119 TGME49_chrV 3074668 3075701 − ID = TGME49_283570; 1839 length = 1033 TGME49_chrVIIa 329088 331013 − ID = TGME49_280540; 1840 length = 1925 TGME49_chrXII 1135859 1136707 − ID = TGME49_219090; 1841 length = 848 TGME49_chrXI 562038 563532 − ID = TGME49_309210; 1842 length = 1494 TGME49_chrXI 5079763 5082015 + ID = TGME49_315930; 1843 length = 2252 TGME49_chrXII 4230010 4231788 + ID = TGME49_248870; 1844 length = 1778 TGME49_chrVIII 347018 350776 + ID = TGME49_229640; 1845 length = 3758 TGME49_chrIX 3368958 3370369 + ID = TGME49_289670; 1846 length = 1411 TGME49_chrVIII 2687436 2690407 − ID = TGME49_233500; 1847 length = 2971 TGME49_chrVIIb 611076 613065 − ID = TGME49_263360; 1848 length = 1989 TGME49_chrVIIb 3970006 3973027 − ID = TGME49_257568; 1849 length = 3021 TGME49_chrVIIb 1325239 1328902 + ID = TGME49_262160; 1850 length = 3663 TGME49_chrVIII 4413113 4415505 − ID = TGME49_271760; 1851 length = 2392 TGME49_chrVIIa 3814503 3816891 + ID = TGME49_201760; 1852 length = 2388 TGME49_chrXI 4058535 4061396 + ID = TGME49_314400; 1853 length = 2861 TGME49_chrXI 1854395 1859046 + ID = TGME49_311210; 1854 length = 4651 TGME49_chrX 4632110 4634094 + ID = TGME49_235140; 1855 length = 1984 TGME49_chrIX 5815296 5819202 + ID = TGME49_306190; 1856 length = 3906 TGME49_chrVIIb 2908955 2910810 − ID = TGME49_259180; 1857 length = 1855 TGME49_chrVIII 2421212 2423837 − ID = TGME49_233100; 1858 length = 2625 TGME49_chrXI 431000 433353 − ID = TGME49_309000; 1859 length = 2353 TGME49_chrXI 2271030 2275657 + ID = TGME49_311770; 1860 length = 4627 TGME49_chrVIII 4332070 4335007 + ID = TGME49_271850; 1861 length = 2937 TGME49_chrXII 4989160 4990606 + ID = TGME49_250020; 1862 length = 1446 TGME49_chrXII 2677358 2679539 + ID = TGME49_246130; 1863 length = 2181 TGME49_chrVIIa 305043 307438 + ID = TGME49_280550; 1864 length = 2395 TGME49_chrXI 4668181 4671233 + ID = TGME49_315360; 1865 length = 3052 TGME49_chrX 2035088 2038686 + ID = TGME49_225790; 1866 length = 3598 TGME49_chrVIIb 3259872 3262590 − ID = TGME49_258690; 1867 length = 2718 TGME49_chrXII 4912829 4914644 − ID = TGME49_249860; 1868 length = 1815 TGME49_chrVI 2440086 2442352 − ID = TGME49_243200; 1869 length = 2266 TGME49_chrVIII 3880336 3884798 + ID = TGME49_272560; 1870 length = 4462 TGME49_chrXII 3831607 3833051 − ID = TGME49_248390; 1871 length = 1444 TGME49_chrXI 2262796 2265505 − ID = TGME49_311760; 1872 length = 2709 TGME49_chrIa 741460 745719 − ID = TGME49_294240; 1873 length = 4259 TGME49_chrIb 1782617 1787380 − ID = TGME49_321470; 1874 length = 4763 TGME49_chrVIIa 1669931 1670876 − ID = TGME49_205020; 1875 length = 945 TGME49_chrVIII 6326491 6329179 − ID = TGME49_268770; 1876 length = 2688 TGME49_chrV 166266 168190 − ID = TGME49_220145; 1877 length = 1924 TGME49_chrIV 576195 580895 − ID = TGME49_320020; 1878 length = 4700 TGME49_chrVIII 1298224 1301679 + ID = TGME49_231175; 1879 length = 3455 TGME49_chrVIIb 4964424 4968613 − ID = TGME49_255250; 1880 length = 4189 TGME49_chrIX 709923 711569 − ID = TGME49_267340; 1881 length = 1646 TGME49_chrX 4556936 4560782 + ID = TGME49_234970; 1882 length = 3846 TGME49_chrVIIb 393977 397643 − ID = TGME49_263690; 1883 length = 3666 TGME49_chrXII 5422931 5424831 − ID = TGME49_251480; 1884 length = 1900 TGME49_chrIX 914298 915352 + ID = TGME49_266880; 1885 length = 1054 TGME49_chrV 428812 432815 + ID = TGME49_220520; 1886 length = 4003 TGME49_chrXI 6404954 6409920 − ID = TGME49_216080; 1887 length = 4966 TGME49_chrII 861618 866482 − ID = TGME49_222080; 1888 length = 4864 TGME49_chrXII 5669867 5671445 + ID = TGME49_251930; 1889 length = 1578 TGME49_chrVI 2532929 2537138 + ID = TGME49_243310; 1890 length = 4209 TGME49_chrIX 3807821 3810806 − ID = TGME49_290640; 1891 length = 2985 TGME49_chrVIIa 901698 904817 − ID = TGME49_206540; 1892 length = 3119 TGME49_chrIX 1847463 1852082 + ID = TGME49_265000; 1893 length = 4619 TGME49_chrVIIa 2454532 2456953 + ID = TGME49_203510; 1894 length = 2421 TGME49_chrVIII 3604698 3606638 + ID = TGME49_273290; 1895 length = 1940 TGME49_chrVIII 2234752 2236893 − ID = TGME49_232700; 1896 length = 2141 TGME49_chrVI 2449321 2450374 + ID = TGME49_243220; 1897 length = 1053 TGME49_chrX 6937184 6938923 + ID = TGME49_215385; 1898 length = 1739 TGME49_chrIX 680988 684814 − ID = TGME49_267380; 1899 length = 3826 TGME49_chrVIIa 2261027 2263156 − ID = TGME49_203760; 1900 length = 2129 TGME49_chrIX 3145275 3148375 − ID = TGME49_289280; 1901 length = 3100 TGME49_chrVIIa 2489722 2491017 + ID = TGME49_203470; 1902 length = 1295 TGME49_chrVIII 1769885 1774294 − ID = TGME49_232020; 1903 length = 4409 TGME49_chrVIIa 3993533 3996332 − ID = TGME49_201160; 1904 length = 2799 TGME49_chrX 4514799 4516300 + ID = TGME49_234660; 1905 length = 1501 TGME49_chrV 860484 863029 − ID = TGME49_213100; 1906 length = 2545 TGME49_chrVIIb 3591281 3593195 − ID = TGME49_258085; 1907 length = 1914 TGME49_chrIV 1514865 1518877 + ID = TGME49_318160; 1908 length = 4012 TGME49_chrX 3279666 3282705 − ID = TGME49_224180; 1909 length = 3039 TGME49_chrVIII 975775 977748 + ID = TGME49_230700; 1910 length = 1973 TGME49_chrVIIb 3085729 3088120 − ID = TGME49_258940; 1911 length = 2391 TGME49_chrXII 529861 532149 + ID = TGME49_308050; 1912 length = 2288 TGME49_chrV 239790 243541 − ID = TGME49_220240; 1913 length = 3751 TGME49_chrII 1461513 1463416 − ID = TGME49_223125; 1914 length = 1903 TGME49_chrXI 5222117 5224159 − ID = TGME49_316280; 1915 length = 2042 TGME49_chrII 1468306 1470065 + ID = TGME49_223140; 1916 length = 1759 TGME49_chrXI 2353715 2358433 + ID = TGME49_311890; 1917 length = 4718 TGME49_chrII 1582123 1586805 + ID = TGME49_297170; 1918 length = 4682 TGME49_chrIX 199072 203223 + ID = TGME49_279400; 1919 length = 4151 TGME49_chrIV 284392 286223 − ID = TGME49_320525; 1920 length = 1831 TGME49_chrIX 4842934 4844771 − ID = TGME49_210370; 1921 length = 1837 TGME49_chrXI 4452167 4456567 − ID = TGME49_314970; 1922 length = 4400 TGME49_chrXI 2499772 2502355 − ID = TGME49_312200; 1923 length = 2583 TGME49_chrIb 890079 892589 − ID = TGME49_208830; 1924 length = 2510 TGME49_chrVIII 1966362 1967945 − ID = TGME49_232230; 1925 length = 1583 TGME49_chrVI 989945 991803 − ID = TGME49_239880; 1926 length = 1858 TGME49_chrVIIb 3518895 3521575 + ID = TGME49_258200; 1927 length = 2680 TGME49_chrV 216186 217667 − ID = TGME49_220208; 1928 length = 1481 TGME49_chrXII 5640276 5641811 + ID = TGME49_251885; 1929 length = 1535 TGME49_chrXII 3826538 3828410 − ID = TGME49_248360; 1930 length = 1872 TGME49_chrIX 736629 737403 + ID = TGME49_267290; 1931 length = 774 TGME49_chrV 578793 583050 − ID = TGME49_212740; 1932 length = 4257 TGME49_chrXII 2886732 2889046 + ID = TGME49_246620; 1933 length = 2314 TGME49_chrXII 4176365 4178211 + ID = TGME49_248800; 1934 length = 1846 TGME49_chrVIII 5063747 5066564 − ID = TGME49_270710; 1935 length = 2817 TGME49_chrV 1907332 1909721 + ID = TGME49_286220; 1936 length = 2389 TGME49_chrXI 3397474 3401749 − ID = TGME49_313440; 1937 length = 4275 TGME49_chrVIIa 3861824 3865091 + ID = TGME49_201670; 1938 length = 3267 TGME49_chrXII 5569684 5571506 − ID = TGME49_251760; 1939 length = 1822 TGME49_chrXII 2225921 2229690 + ID = TGME49_217920; 1940 length = 3769 TGME49_chrIX 3307872 3310644 + ID = TGME49_289570; 1941 length = 2772 TGME49_chrIa 156682 159073 + ID = TGME49_293200; 1942 length = 2391 TGME49_chrXII 3881332 3885535 − ID = TGME49_248470; 1943 length = 4203 TGME49_chrX 418777 421046 − ID = TGME49_228330; 1944 length = 2269 TGME49_chrV 2274025 2276420 − ID = TGME49_285720; 1945 length = 2395 TGME49_chrXI 2992217 2995109 − ID = TGME49_312940; 1946 length = 2892 TGME49_chrIa 390048 391767 − ID = TGME49_293520; 1947 length = 1719 TGME49_chrVIII 6445709 6450718 − ID = TGME49_268450; 1948 length = 5009 TGME49_chrVIIa 3924398 3927902 − ID = TGME49_201270; 1949 length = 3504 TGME49_chrIX 2612526 2615415 + ID = TGME49_288560; 1950 length = 2889 TGME49_chrIX 5394025 5396129 − ID = TGME49_305450; 1951 length = 2104 TGME49_chrVI 2449321 2454332 + ID = TGME49_243240; 1952 length = 5011 TGME49_chrX 1141678 1144996 + ID = TGME49_227000; 1953 length = 3318 TGME49_chrVIIa 3580633 3582769 − ID = TGME49_202140; 1954 length = 2136 TGME49_chrVIII 712149 714535 + ID = TGME49_230340; 1955 length = 2386 TGME49_chrX 653775 657724 − ID = TGME49_228050; 1956 length = 3949 TGME49_chrX 1529076 1530823 − ID = TGME49_226580; 1957 length = 1747 TGME49_chrVIIa 3334651 3338417 − ID = TGME49_202430; 1958 length = 3766 TGME49_chrVIIb 2163201 2165337 − ID = TGME49_260570; 1959 length = 2136 TGME49_chrVIIb 1043848 1045795 + ID = TGME49_262740; 1960 length = 1947 TGME49_chrX 1311053 1316055 + ID = TGME49_226825; 1961 length = 5002 TGME49_chrVIII 3977496 3979941 − ID = TGME49_272430; 1962 length = 2445 TGME49_chrV 1789192 1791334 + ID = TGME49_286530; 1963 length = 2142 TGME49_chrVIIb 4173922 4175290 + ID = TGME49_257170; 1964 length = 1368 TGME49_chrXI 4591396 4593178 + ID = TGME49_315230; 1965 length = 1782 TGME49_chrVIII 249237 251305 − ID = TGME49_229420; 1966 length = 2068 TGME49_chrV 646486 648649 − ID = TGME49_212840; 1967 length = 2163 TGME49_chrXI 1120330 1122240 + ID = TGME49_310180; 1968 length = 1910 TGME49_chrXI 5575321 5577263 − ID = TGME49_316760; 1969 length = 1942 TGME49_chrVIII 2874613 2878765 − ID = TGME49_233870; 1970 length = 4152 TGME49_chrXII 5511516 5512810 + ID = TGME49_251650; 1971 length = 1294 TGME49_chrIV 1628157 1629047 + ID = TGME49_211675; 1972 length = 890 TGME49_chrV 1422629 1425901 − ID = TGME49_213900; 1973 length = 3272 TGME49_chrVIIa 186501 190276 + ID = TGME49_280670; 1974 length = 3775 TGME49_chrVIIa 929557 930012 − ID = TGME49_206500; 1975 length = 455 TGME49_chrIX 2971270 2973519 + ID = TGME49_289080; 1976 length = 2249 TGME49_chrVIII 3930340 3931981 − ID = TGME49_272510; 1977 length = 1641 TGME49_chrXI 181107 183028 − ID = TGME49_306930; 1978 length = 1921 TGME49_chrIX 1649663 1652849 + ID = TGME49_265255; 1979 length = 3186 TGME49_chrXII 1073927 1076130 + ID = TGME49_219200; 1980 length = 2203 TGME49_chrIV 2471037 2473860 + ID = TGME49_301430; 1981 length = 2823 TGME49_chrXII 6364866 6366334 + ID = TGME49_278005; 1982 length = 1468 TGME49_chrIb 842071 845707 − ID = TGME49_208740; 1983 length = 3636 TGME49_chrVI 790118 795087 + ID = TGME49_239600; 1984 length = 4969 TGME49_chrX 1424298 1426804 + ID = TGME49_226700; 1985 length = 2506 TGME49_chrV 560109 564542 − ID = TGME49_287490; 1986 length = 4433 TGME49_chrX 2483670 2486271 + ID = TGME49_225120; 1987 length = 2601 TGME49_chrVIIa 1393725 1398244 − ID = TGME49_205460; 1988 length = 4519 TGME49_chrXII 1092592 1094200 + ID = TGME49_219175; 1989 length = 1608 TGME49_chrX 705828 707714 − ID = TGME49_227960; 1990 length = 1886 TGME49_chrIX 4404496 4406990 − ID = TGME49_291910; 1991 length = 2494 TGME49_chrX 6998185 6999653 − ID = TGME49_215510; 1992 length = 1468 TGME49_chrX 4525519 4527356 + ID = TGME49_234680; 1993 length = 1837 TGME49_chrX 1364413 1366308 + ID = TGME49_226780; 1994 length = 1895 TGME49_chrVIIb 1434482 1435459 − ID = TGME49_262000; 1995 length = 977 TGME49_chrVIII 3198328 3202978 − ID = TGME49_273885; 1996 length = 4650 TGME49_chrVIII 5891946 5894191 + ID = TGME49_269320; 1997 length = 2245 TGME49_chrII 1801273 1805605 + ID = TGME49_297470; 1998 length = 4332 TGME49_chrII 1583366 1587369 − ID = TGME49_297160; 1999 length = 4003 TGME49_chrXI 1015690 1017565 − ID = TGME49_310030; 2000 length = 1875 TGME49_chrVIII 284128 286310 + ID = TGME49_229470; 2001 length = 2182 TGME49_chrIV 206127 211040 − ID = TGME49_320610; 2002 length = 4913 TGME49_chrIV 954032 956564 − ID = TGME49_319510; 2003 length = 2532 TGME49_chrX 1102477 1104098 − ID = TGME49_227080; 2004 length = 1621 TGME49_chrIX 3667981 3670156 − ID = TGME49_290250; 2005 length = 2175 TGME49_chrVIII 6519638 6522878 + ID = TGME49_268360; 2006 length = 3240 TGME49_chrXI 5440111 5443988 − ID = TGME49_316620; 2007 length = 3877 TGME49_chrVIIa 2177416 2179962 + ID = TGME49_203840; 2008 length = 2546 TGME49_chrVIII 5084209 5085825 + ID = TGME49_270680; 2009 length = 1616 TGME49_chrXI 2995464 2997405 + ID = TGME49_312960; 2010 length = 1941 TGME49_chrII 1625923 1628671 + ID = TGME49_297230; 2011 length = 2748 TGME49_chrXI 1618900 1619991 + ID = TGME49_310830; 2012 length = 1091 TGME49_chrXII 6751504 6754864 − ID = TGME49_277060; 2013 length = 3360 TGME49_chrXI 6165715 6168615 + ID = TGME49_216410; 2014 length = 2900 TGME49_chrV 2636647 2639120 + ID = TGME49_284645; 2015 length = 2473 TGME49_chrVIIb 4473497 4476055 + ID = TGME49_256770; 2016 length = 2558 TGME49_chrVIII 5253838 5255754 − ID = TGME49_270350; 2017 length = 1916 TGME49_chrVI 995195 999093 − ID = TGME49_239890; 2018 length = 3898 TGME49_chrVI 1546743 1551741 − ID = TGME49_240900; 2019 length = 4998 TGME49_chrVIIb 3570823 3572905 − ID = TGME49_258110; 2020 length = 2082 TGME49_chrIX 1687388 1690438 + ID = TGME49_265220; 2021 length = 3050 TGME49_chrVIII 1861928 1864368 + ID = TGME49_232120; 2022 length = 2440 TGME49_chrV 488616 490907 + ID = TGME49_220620; 2023 length = 2291 TGME49_chrVI 3402464 3405837 − ID = TGME49_244620; 2024 length = 3373 TGME49_chrV 469162 471286 + ID = TGME49_220585; 2025 length = 2124 TGME49_chrX 448104 450711 − ID = TGME49_228270; 2026 length = 2607 TGME49_chrIa 840385 841380 − ID = TGME49_294350; 2027 length = 995 TGME49_chrXI 1642170 1643093 + ID = TGME49_310875; 2028 length = 923 TGME49_chrVIII 4995719 4997442 + ID = TGME49_270780; 2029 length = 1723 TGME49_chrVI 927570 932508 − ID = TGME49_239800; 2030 length = 4938 TGME49_chrVIIa 1843313 1845988 + ID = TGME49_204370; 2031 length = 2675 TGME49_chrX 4549606 4553931 + ID = TGME49_234940; 2032 length = 4325 TGME49_chrVI 1708785 1711030 + ID = TGME49_241610; 2033 length = 2245 TGME49_chrX 4938972 4940429 − ID = TGME49_235540; 2034 length = 1457 TGME49_chrVIIb 164856 169420 + ID = TGME49_264120; 2035 length = 4564 TGME49_chrIX 4027598 4029731 + ID = TGME49_291000; 2036 length = 2133 TGME49_chrVIIa 1419599 1421687 + ID = TGME49_205402; 2037 length = 2088 TGME49_chrXI 436362 437746 + ID = TGME49_309020; 2038 length = 1384 TGME49_chrXI 5176299 5179174 + ID = TGME49_316190; 2039 length = 2875 TGME49_chrVIIb 2712120 2714104 − ID = TGME49_259690; 2040 length = 1984 TGME49_chrIb 1450314 1450964 + ID = TGME49_209780; 2041 length = 650 TGME49_chrXII 5939359 5941323 − ID = TGME49_278680; 2042 length = 1964 TGME49_chrXII 602054 603985 − ID = TGME49_219850; 2043 length = 1931 TGME49_chrIX 4431878 4435031 + ID = TGME49_291960; 2044 length = 3153 TGME49_chrV 2167500 2172395 − ID = TGME49_285860; 2045 length = 4895 TGME49_chrIX 6049752 6053318 + ID = TGME49_306400; 2046 length = 3566 TGME49_chrVIIb 1662568 1663864 − ID = TGME49_261550; 2047 length = 1296 TGME49_chrX 2807197 2808264 + ID = TGME49_224820; 2048 length = 1067 TGME49_chrIX 1941820 1943728 − ID = TGME49_264875; 2049 length = 1908 TGME49_chrVI 41637 46647 + ID = TGME49_238070; 2050 length = 5010 TGME49_chrXI 6420835 6425390 − ID = TGME49_216070; 2051 length = 4555 TGME49_chrIX 469404 472283 + ID = TGME49_267670; 2052 length = 2879 TGME49_chrX 6007176 6009045 − ID = TGME49_237595; 2053 length = 1869 TGME49_chrXI 5608472 5610173 − ID = TGME49_316900; 2054 length = 1701 TGME49_chrX 6171995 6176026 + ID = TGME49_214250; 2055 length = 4031 TGME49_chrIX 2786348 2787500 − ID = TGME49_288870; 2056 length = 1152 TGME49_chrIX 4071340 4075503 − ID = TGME49_291020; 2057 length = 4163 TGME49_chrXI 362611 365152 − ID = TGME49_308920; 2058 length = 2541 TGME49_chrXII 6038102 6039598 − ID = TGME49_278540; 2059 length = 1496 TGME49_chrIa 1383866 1386224 + ID = TGME49_295080; 2060 length = 2358 TGME49_chrXI 1255210 1257092 + ID = TGME49_310320; 2061 length = 1882 TGME49_chrX 5800930 5803170 − ID = TGME49_237230; 2062 length = 2240 TGME49_chrIX 3725934 3727613 + ID = TGME49_290460; 2063 length = 1679 TGME49_chrVI 831846 833871 − ID = TGME49_239680; 2064 length = 2025 TGME49_chrX 184156 186759 − ID = TGME49_228730; 2065 length = 2603 TGME49_chrIX 608936 612060 − ID = TGME49_267510; 2066 length = 3124 TGME49_chrVIII 2604042 2605811 + ID = TGME49_233350; 2067 length = 1769 TGME49_chrVI 3370292 3371967 + ID = TGME49_244580; 2068 length = 1675 TGME49_chrVIIb 4313028 4313787 − ID = TGME49_256975; 2069 length = 759 TGME49_chrXI 5775427 5777232 − ID = TGME49_216960; 2070 length = 1805 TGME49_chrVIIb 2103737 2106170 − ID = TGME49_260640; 2071 length = 2433 TGME49_chrX 1795604 1797542 + ID = TGME49_226100; 2072 length = 1938 TGME49_chrX 418101 419981 + ID = TGME49_228320; 2073 length = 1880 TGME49_chrXI 1340616 1343000 + ID = TGME49_310440; 2074 length = 2384 TGME49_chrIX 3355308 3357831 + ID = TGME49_289630; 2075 length = 2523 TGME49_chrVIII 2192583 2194733 + ID = TGME49_232620; 2076 length = 2150 TGME49_chrVIIb 4636561 4638383 − ID = TGME49_255900; 2077 length = 1822 TGME49_chrVIII 5588163 5590158 + ID = TGME49_269820; 2078 length = 1995 TGME49_chrVI 3247506 3250212 − ID = TGME49_244408; 2079 length = 2706 TGME49_chrVIIa 2051496 2056236 − ID = TGME49_204010; 2080 length = 4740 TGME49_chrVIII 491985 494558 + ID = TGME49_229980; 2081 length = 2573 TGME49_chrVIIa 2056536 2058106 + ID = TGME49_203985; 2082 length = 1570 TGME49_chrVIIa 140276 144404 + ID = TGME49_280725; 2083 length = 4128 TGME49_chrVIII 2250698 2252771 − ID = TGME49_232750; 2084 length = 2073 TGME49_chrVIII 5887047 5889397 − ID = TGME49_269340; 2085 length = 2350 TGME49_chrXI 1052803 1054295 − ID = TGME49_310090; 2086 length = 1492 TGME49_chrVI 1279772 1281594 + ID = TGME49_240440; 2087 length = 1822 TGME49_chrVIIb 756456 758017 − ID = TGME49_263160; 2088 length = 1561 TGME49_chrII 1811993 1815135 + ID = TGME49_297480; 2089 length = 3142 TGME49_chrVIIa 990948 995424 − ID = TGME49_206430; 2090 length = 4476 TGME49_chrV 2986113 2990861 − ID = TGME49_283770; 2091 length = 4748 TGME49_chrXII 850493 852277 − ID = TGME49_219560; 2092 length = 1784 TGME49_chrIV 1344162 1349005 − ID = TGME49_318430; 2093 length = 4843 TGME49_chrVIIb 1056333 1059103 − ID = TGME49_262730; 2094 length = 2770 TGME49_chrVIII 4661713 4663360 − ID = TGME49_271170; 2095 length = 1647 TGME49_chrXI 5942768 5945248 + ID = TGME49_216720; 2096 length = 2480 TGME49_chrXI 1779520 1783053 + ID = TGME49_311075; 2097 length = 3533 TGME49_chrIb 1820664 1822422 + ID = TGME49_321420; 2098 length = 1758 TGME49_chrX 1944153 1948496 + ID = TGME49_225900; 2099 length = 4343 TGME49_chrVIIa 1201335 1202972 + ID = TGME49_205710; 2100 length = 1637 TGME49_chrXI 4872334 4874729 − ID = TGME49_315640; 2101 length = 2395 TGME49_chrVIII 1554633 1557549 + ID = TGME49_231815; 2102 length = 2916 TGME49_chrXI 3051809 3056712 + ID = TGME49_313030; 2103 length = 4903 TGME49_chrX 2840250 2842141 − ID = TGME49_224750; 2104 length = 1891 TGME49_chrIX 2419221 2423061 + ID = TGME49_288260; 2105 length = 3840 TGME49_chrII 443749 446045 − ID = TGME49_221560; 2106 length = 2296 TGME49_chrVIIb 1969192 1973085 − ID = TGME49_261018; 2107 length = 3893 TGME49_chrX 2971389 2973789 − ID = TGME49_224575; 2108 length = 2400 TGME49_chrIX 509919 513149 − ID = TGME49_267642; 2109 length = 3230 TGME49_chrXI 5787432 5789807 − ID = TGME49_216930; 2110 length = 2375 TGME49_chrIX 4469028 4471277 − ID = TGME49_292000; 2111 length = 2249 TGME49_chrIX 4276237 4279338 − ID = TGME49_291360; 2112 length = 3101 TGME49_chrVIIb 2342177 2343737 − ID = TGME49_260360; 2113 length = 1560 TGME49_chrXI 1287445 1292319 + ID = TGME49_310360; 2114 length = 4874 TGME49_chrXII 5070692 5074348 − ID = TGME49_250360; 2115 length = 3656 TGME49_chrVIIb 1569559 1572751 + ID = TGME49_261710; 2116 length = 3192 TGME49_chrX 2583373 2586162 − ID = TGME49_225020; 2117 length = 2789 TGME49_chrVIII 1386339 1390571 − ID = TGME49_231370; 2118 length = 4232 TGME49_chrIX 3341749 3343589 − ID = TGME49_289600; 2119 length = 1840 TGME49_chrIX 4852500 4855230 + ID = TGME49_210345; 2120 length = 2730 TGME49_chrVIII 1999232 2003285 − ID = TGME49_232300; 2121 length = 4053 TGME49_chrX 1217918 1218840 + ID = TGME49_226930; 2122 length = 922 TGME49_chrIX 393414 395802 + ID = TGME49_267740; 2123 length = 2388 TGME49_chrVIII 2239831 2241664 − ID = TGME49_232720; 2124 length = 1833 TGME49_chrX 1778082 1780845 + ID = TGME49_226220; 2125 length = 2763 TGME49_chrVIIb 4325180 4329892 − ID = TGME49_256970; 2126 length = 4712 TGME49_chrIV 185525 187612 + ID = TGME49_320630; 2127 length = 2087 TGME49_chrXII 5016450 5018497 + ID = TGME49_250090; 2128 length = 2047 TGME49_chrIX 5971552 5972595 + ID = TGME49_306334; 2129 length = 1043 TGME49_chrIV 1654904 1658845 − ID = TGME49_211640; 2130 length = 3941 TGME49_chrIV 1691102 1693242 + ID = TGME49_211470; 2131 length = 2140 TGME49_chrVIII 1440721 1442757 + ID = TGME49_231460; 2132 length = 2036 TGME49_chrXI 2173066 2177892 − ID = TGME49_311640; 2133 length = 4826 TGME49_chrX 5232720 5234701 + ID = TGME49_236000; 2134 length = 1981 TGME49_chrXI 2361325 2365388 + ID = TGME49_311905; 2135 length = 4063 TGME49_chrVIII 2482479 2486633 − ID = TGME49_233180; 2136 length = 4154 TGME49_chrXII 205121 208744 − ID = TGME49_300120; 2137 length = 3623 TGME49_chrXII 5293378 5296947 − ID = TGME49_250870; 2138 length = 3569 TGME49_chrIX 4582773 4584034 − ID = TGME49_292150; 2139 length = 1261 TGME49_chrVIIb 2118657 2123522 − ID = TGME49_260620; 2140 length = 4865 TGME49_chrXII 3632829 3637477 + ID = TGME49_247950; 2141 length = 4648 TGME49_chrVIII 3416508 3419960 + ID = TGME49_273520; 2142 length = 3452 TGME49_chrX 7007085 7010674 − ID = TGME49_215540; 2143 length = 3589 TGME49_chrX 2610836 2612776 − ID = TGME49_224990; 2144 length = 1940 TGME49_chrXII 286679 290951 + ID = TGME49_300000; 2145 length = 4272 TGME49_chrXI 1067581 1069045 − ID = TGME49_310122; 2146 length = 1464 TGME49_chrVIIa 2523724 2528425 − ID = TGME49_203390; 2147 length = 4701 TGME49_chrVIII 6368584 6372245 + ID = TGME49_268670; 2148 length = 3661 TGME49_chrIX 2379171 2383345 + ID = TGME49_288210; 2149 length = 4174 TGME49_chrX 6247060 6249835 − ID = TGME49_214310; 2150 length = 2775 TGME49_chrX 4410724 4415344 − ID = TGME49_234470; 2151 length = 4620 TGME49_chrVIII 483790 485820 + ID = TGME49_229950; 2152 length = 2030 TGME49_chrVIIa 1207940 1212921 + ID = TGME49_205690; 2153 length = 4981 TGME49_chrIV 548750 550949 + ID = TGME49_320050; 2154 length = 2199 TGME49_chrXI 3335719 3337418 + ID = TGME49_313390; 2155 length = 1699 TGME49_chrX 4499729 4504428 + ID = TGME49_234625; 2156 length = 4699 TGME49_chrIX 1306171 1308162 − ID = TGME49_266100; 2157 length = 1991 TGME49_chrX 4987373 4988579 + ID = TGME49_235620; 2158 length = 1206 TGME49_chrII 2049153 2053496 − ID = TGME49_297820; 2159 length = 4343 TGME49_chrIb 1005392 1010351 − ID = TGME49_209040; 2160 length = 4959 TGME49_chrIV 1416910 1419099 + ID = TGME49_318320; 2161 length = 2189 TGME49_chrV 1823713 1827597 − ID = TGME49_286460; 2162 length = 3884 TGME49_chrXII 6505888 6507354 − ID = TGME49_277800; 2163 length = 1466 TGME49_chrXII 3889671 3891930 − ID = TGME49_248490; 2164 length = 2259 TGME49_chrVIIa 1516113 1517866 − ID = TGME49_205250; 2165 length = 1753 TGME49_chrVIIa 4147257 4149471 − ID = TGME49_281480; 2166 length = 2214 TGME49_chrVIII 2668587 2671322 + ID = TGME49_233480; 2167 length = 2735 TGME49_chrIX 5608315 5609770 + ID = TGME49_305830; 2168 length = 1455 TGME49_chrX 5460615 5465206 − ID = TGME49_236630; 2169 length = 4591 TGME49_chrIb 446581 448900 − ID = TGME49_207930; 2170 length = 2319 TGME49_chrVI 2958204 2962910 + ID = TGME49_244020; 2171 length = 4706 TGME49_chrXI 2553635 2555730 − ID = TGME49_312260; 2172 length = 2095 TGME49_chrVIII 5353669 5357579 + ID = TGME49_270170; 2173 length = 3910 TGME49_chrXII 224079 225774 + ID = TGME49_300090; 2174 length = 1695 TGME49_chrVIIb 4614928 4619845 − ID = TGME49_255960; 2175 length = 4917 TGME49_chrVIII 1473271 1475198 − ID = TGME49_231480; 2176 length = 1927 TGME49_chrVIIa 2707675 2711017 + ID = TGME49_203170; 2177 length = 3342 TGME49_chrX 4325394 4328594 + ID = TGME49_234375; 2178 length = 3200 TGME49_chrVIIb 201826 206450 + ID = TGME49_264075; 2179 length = 4624 TGME49_chrXI 3987704 3989680 − ID = TGME49_314280; 2180 length = 1976 TGME49_chrIV 2431107 2432795 + ID = TGME49_301390; 2181 length = 1688 TGME49_chrVIIb 1554047 1557249 − ID = TGME49_261740; 2182 length = 3202 TGME49_chrXI 6077898 6080164 + ID = TGME49_216570; 2183 length = 2266 TGME49_chrIX 5907877 5909447 − ID = TGME49_306280; 2184 length = 1570 TGME49_chrIX 1291274 1293712 + ID = TGME49_266110; 2185 length = 2438 TGME49_chrIb 3431 5000 + ID = TGME49_207360; 2186 length = 1569 TGME49_chrIV 749326 751746 + ID = TGME49_319740; 2187 length = 2420 TGME49_chrVIIb 1574484 1575737 + ID = TGME49_261700; 2188 length = 1253 TGME49_chrVI 1338921 1343149 + ID = TGME49_240630; 2189 length = 4228 TGME49_chrXII 5539534 5541403 − ID = TGME49_251720; 2190 length = 1869 TGME49_chrVIIb 4896623 4898784 + ID = TGME49_255330; 2191 length = 2161 TGME49_chrXII 4733817 4737060 + ID = TGME49_249690; 2192 length = 3243 TGME49_chrII 1383871 1385210 + ID = TGME49_223050; 2193 length = 1339 TGME49_chrXI 4617346 4620622 + ID = TGME49_315280; 2194 length = 3276 TGME49_chrXI 1870125 1871822 + ID = TGME49_311220; 2195 length = 1697 TGME49_chrXII 3843245 3845735 + ID = TGME49_248425; 2196 length = 2490 TGME49_chrXII 5389506 5393276 + ID = TGME49_251450; 2197 length = 3770 TGME49_chrVIII 5980495 5982851 − ID = TGME49_269228; 2198 length = 2356 TGME49_chrIV 1479718 1482540 − ID = TGME49_318220; 2199 length = 2822 TGME49_chrVIIa 3910752 3912895 − ID = TGME49_201390; 2200 length = 2143 TGME49_chrVI 2860199 2862974 − ID = TGME49_243790; 2201 length = 2775 TGME49_chrVIIa 2178513 2180276 − ID = TGME49_203860; 2202 length = 1763 TGME49_chrII 1341931 1344535 + ID = TGME49_222970; 2203 length = 2604 TGME49_chrXII 4348700 4350687 − ID = TGME49_249160; 2204 length = 1987 TGME49_chrV 1817252 1819572 − ID = TGME49_286485; 2205 length = 2320 TGME49_chrIX 4096568 4099371 + ID = TGME49_291070; 2206 length = 2803 TGME49_chrV 1456377 1459175 − ID = TGME49_213940; 2207 length = 2798 TGME49_chrIa 1128268 1130676 − ID = TGME49_294760; 2208 length = 2408 TGME49_chrXII 112149 115996 + ID = TGME49_300270; 2209 length = 3847 TGME49_chrIa 1141182 1145699 − ID = TGME49_294780; 2210 length = 4517 TGME49_chrIa 684768 686694 − ID = TGME49_294180; 2211 length = 1926 TGME49_chrXII 1982533 1984559 − ID = TGME49_217665; 2212 length = 2026 TGME49_chrVIIb 136836 141095 − ID = TGME49_264150; 2213 length = 4259 TGME49_chrIX 3644889 3646816 − ID = TGME49_290200; 2214 length = 1927 TGME49_chrXI 3416844 3420688 + ID = TGME49_313475; 2215 length = 3844 TGME49_chrXII 5558311 5563031 + ID = TGME49_251750; 2216 length = 4720 TGME49_chrVIII 3591126 3594224 − ID = TGME49_273330; 2217 length = 3098 TGME49_chrXI 1907165 1911891 + ID = TGME49_311250; 2218 length = 4726 TGME49_chrIb 606581 608427 + ID = TGME49_208320; 2219 length = 1846 TGME49_chrIV 317723 320840 + ID = TGME49_320470; 2220 length = 3117 TGME49_chrIa 1231366 1233810 + ID = TGME49_294870; 2221 length = 2444 TGME49_chrV 799204 803341 + ID = TGME49_213030; 2222 length = 4137 TGME49_chrXII 4141267 4145015 − ID = TGME49_248740; 2223 length = 3748 TGME49_chrVIII 6831032 6832955 − ID = TGME49_200370; 2224 length = 1923 TGME49_chrVIII 5814181 5817773 + ID = TGME49_269417; 2225 length = 3592 TGME49_chrIa 288432 290836 + ID = TGME49_293380; 2226 length = 2404 TGME49_chrX 375771 377308 + ID = TGME49_228360; 2227 length = 1537 TGME49_chrVIIa 2817075 2820018 + ID = TGME49_203070; 2228 length = 2943 TGME49_chrIX 2642426 2644741 + ID = TGME49_288630; 2229 length = 2315 TGME49_chrVIIa 3778324 3780703 − ID = TGME49_201810; 2230 length = 2379 TGME49_chrXI 2136968 2138370 − ID = TGME49_311500; 2231 length = 1402 TGME49_chrX 6746604 6749287 + ID = TGME49_215090; 2232 length = 2683 TGME49_chrVIIa 428379 432545 − ID = TGME49_280420; 2233 length = 4166 TGME49_chrVI 3187139 3188303 + ID = TGME49_244320; 2234 length = 1164 TGME49_chrVI 1463601 1465416 − ID = TGME49_240830; 2235 length = 1815 TGME49_chrX 6273860 6275989 + ID = TGME49_214400; 2236 length = 2129 TGME49_chrVI 2220309 2222591 + ID = TGME49_242740; 2237 length = 2282 TGME49_chrIb 1351872 1355146 + ID = TGME49_209590; 2238 length = 3274 TGME49_chrVIII 294473 299452 + ID = TGME49_229490; 2239 length = 4979 TGME49_chrIV 1996453 1998125 + ID = TGME49_210970; 2240 length = 1672 TGME49_chrVIII 2608007 2611227 + ID = TGME49_233370; 2241 length = 3220 TGME49_chrVIIa 3795393 3798765 + ID = TGME49_201775; 2242 length = 3372 TGME49_chrIa 1293826 1295850 + ID = TGME49_294970; 2243 length = 2024 TGME49_chrIX 4535750 4537308 − ID = TGME49_292070; 2244 length = 1558 TGME49_chrVIIa 2279952 2283671 − ID = TGME49_203740; 2245 length = 3719 TGME49_chrVIIa 485370 487434 + ID = TGME49_280380; 2246 length = 2064 TGME49_chrXI 1095580 1099919 + ID = TGME49_310160; 2247 length = 4339 TGME49_chrVIIb 2166762 2169888 + ID = TGME49_260540; 2248 length = 3126 TGME49_chrX 5492381 5494853 + ID = TGME49_236780; 2249 length = 2472 TGME49_chrVIIa 525141 528720 − ID = TGME49_304490; 2250 length = 3579 TGME49_chrXII 1251462 1253195 + ID = TGME49_218840; 2251 length = 1733 TGME49_chrVIIb 1044560 1046178 − ID = TGME49_262750; 2252 length = 1618 TGME49_chrXII 4941426 4942964 + ID = TGME49_249920; 2253 length = 1538 TGME49_chrVIIb 1995879 1997531 − ID = TGME49_260870; 2254 length = 1652 TGME49_chrXI 4299258 4301184 − ID = TGME49_314780; 2255 length = 1926 TGME49_chrII 1769905 1774752 − ID = TGME49_297420; 2256 length = 4847 TGME49_chrIb 1320040 1321949 − ID = TGME49_209540; 2257 length = 1909 TGME49_chrIX 6177117 6181474 − ID = TGME49_306550; 2258 length = 4357 TGME49_chrV 1725092 1727430 + ID = TGME49_286680; 2259 length = 2338 TGME49_chrVI 811913 814755 + ID = TGME49_239630; 2260 length = 2842 TGME49_chrIX 3876282 3878405 + ID = TGME49_290840; 2261 length = 2123 TGME49_chrII 1693029 1695406 − ID = TGME49_297330; 2262 length = 2377 TGME49_chrIb 1214022 1218129 + ID = TGME49_209440; 2263 length = 4107 TGME49_chrVIII 1574303 1578976 + ID = TGME49_231840; 2264 length = 4673 TGME49_chrVIIb 4914243 4916993 + ID = TGME49_255300; 2265 length = 2750 TGME49_chrXI 1745014 1749860 − ID = TGME49_311030; 2266 length = 4846 TGME49_chrVIII 4131896 4134904 − ID = TGME49_272230; 2267 length = 3008 TGME49_chrXI 186373 190635 + ID = TGME49_306910; 2268 length = 4262 TGME49_chrVIII 4969459 4972682 + ID = TGME49_270820; 2269 length = 3223 TGME49_chrII 252286 255240 − ID = TGME49_221320; 2270 length = 2954 TGME49_chrXII 4665307 4667213 + ID = TGME49_249590; 2271 length = 1906 TGME49_chrXII 183074 185954 + ID = TGME49_300140; 2272 length = 2880 TGME49_chrX 2107642 2109483 − ID = TGME49_225730; 2273 length = 1841 TGME49_chrVIII 5084209 5087859 + ID = TGME49_270670; 2274 length = 3650 TGME49_chrVI 3141338 3146169 − ID = TGME49_244250; 2275 length = 4831 TGME49_chrIX 1641728 1646063 + ID = TGME49_265260; 2276 length = 4335 TGME49_chrIb 1625087 1627665 − ID = TGME49_321700; 2277 length = 2578 TGME49_chrII 1708595 1711391 + ID = TGME49_297360; 2278 length = 2796 TGME49_chrXII 2561570 2563897 + ID = TGME49_245770; 2279 length = 2327 TGME49_chrXI 3662083 3664424 − ID = TGME49_313750; 2280 length = 2341 TGME49_chrIX 2678976 2683389 + ID = TGME49_288700; 2281 length = 4413 TGME49_chrVIIa 2452533 2454348 − ID = TGME49_203520; 2282 length = 1815 TGME49_chrVIII 371670 372973 − ID = TGME49_229660; 2283 length = 1303 TGME49_chrVIII 1338333 1339664 − ID = TGME49_231215; 2284 length = 1331 TGME49_chrXI 2393435 2396761 + ID = TGME49_312050; 2285 length = 3326 TGME49_chrVIIb 4834044 4836547 − ID = TGME49_255430; 2286 length = 2503 TGME49_chrIb 454627 456429 − ID = TGME49_207940; 2287 length = 1802 TGME49_chrXII 2364575 2368999 + ID = TGME49_245560; 2288 length = 4424 TGME49_chrIV 290608 295448 + ID = TGME49_320500; 2289 length = 4840 TGME49_chrX 2647792 2650609 + ID = TGME49_224940; 2290 length = 2817 TGME49_chrII 595002 596475 − ID = TGME49_221720; 2291 length = 1473 TGME49_chrV 6880 10388 − ID = TGME49_296121; 2292 length = 3508 TGME49_chrX 4938563 4939819 + ID = TGME49_235550; 2293 length = 1256 TGME49_chrII 24693 25319 − ID = TGME49_220850; 2294 length = 626 TGME49_chrXII 6568190 6570515 − ID = TGME49_277700; 2295 length = 2325 TGME49_chrIV 2058603 2061707 + ID = TGME49_210787; 2296 length = 3104 TGME49_chrX 4451079 4454735 − ID = TGME49_234550; 2297 length = 3656 TGME49_chrX 155871 160694 − ID = TGME49_228760; 2298 length = 4823 TGME49_chrX 7041981 7044359 − ID = TGME49_215590; 2299 length = 2378 TGME49_chrVIIb 1979166 1981300 − ID = TGME49_261010; 2300 length = 2134 TGME49_chrVIIa 266318 267937 + ID = TGME49_280605; 2301 length = 1619 TGME49_chrVIII 2855573 2856668 + ID = TGME49_233860; 2302 length = 1095 TGME49_chrIb 609246 614107 + ID = TGME49_208340; 2303 length = 4861 TGME49_chrX 6384134 6388240 − ID = TGME49_214580; 2304 length = 4106 TGME49_chrVI 280442 282228 + ID = TGME49_238880; 2305 length = 1786 TGME49_chrIX 1848942 1852708 − ID = TGME49_265005; 2306 length = 3766 TGME49_chrX 5418981 5422356 − ID = TGME49_236550; 2307 length = 3375 TGME49_chrIa 1274681 1276904 + ID = TGME49_294930; 2308 length = 2223 TGME49_chrIa 665674 667870 − ID = TGME49_294050; 2309 length = 2196 TGME49_chrVIIb 2761844 2763517 + ID = TGME49_259580; 2310 length = 1673 TGME49_chrIV 1596497 1598239 + ID = TGME49_211695; 2311 length = 1742 TGME49_chrVIII 2332258 2334583 − ID = TGME49_233000; 2312 length = 2325 TGME49_chrVIIb 3451188 3453211 − ID = TGME49_258370; 2313 length = 2023 TGME49_chrIX 5257875 5259734 + ID = TGME49_305160; 2314 length = 1859 TGME49_chrVIII 5392733 5393889 − ID = TGME49_270130; 2315 length = 1156 TGME49_chrXI 5688551 5689284 − ID = TGME49_217178; 2316 length = 733 TGME49_chrIa 1150051 1152041 − ID = TGME49_294800; 2317 length = 1990 TGME49_chrVIIa 691948 694230 − ID = TGME49_304755; 2318 length = 2282 TGME49_chrX 4196707 4198737 + ID = TGME49_234220; 2319 length = 2030 TGME49_chrVI 709612 711661 − ID = TGME49_239480; 2320 length = 2049 TGME49_chrXII 2645668 2648078 − ID = TGME49_246070; 2321 length = 2410 TGME49_chrVIIb 381484 385908 + ID = TGME49_263700; 2322 length = 4424 TGME49_chrXI 3822805 3823979 + ID = TGME49_313940; 2323 length = 1174 TGME49_chrVIII 5492973 5494998 − ID = TGME49_269970; 2324 length = 2025 TGME49_chrII 1955364 1959181 − ID = TGME49_297725; 2325 length = 3817 TGME49_chrVIIa 4402459 4404312 + ID = TGME49_282150; 2326 length = 1853 TGME49_chrX 3723634 3724688 − ID = TGME49_223590; 2327 length = 1054 TGME49_chrX 3023442 3025405 − ID = TGME49_224510; 2328 length = 1963 TGME49_chrVIII 1956674 1958845 − ID = TGME49_232210; 2329 length = 2171 TGME49_chrIX 2177881 2182679 + ID = TGME49_264600; 2330 length = 4798 TGME49_chrVI 3228134 3231037 − ID = TGME49_244380; 2331 length = 2903 TGME49_chrXII 161554 164207 + ID = TGME49_300190; 2332 length = 2653 TGME49_chrV 2386955 2388910 − ID = TGME49_285490; 2333 length = 1955 TGME49_chrXI 5923806 5928393 − ID = TGME49_216750; 2334 length = 4587 TGME49_chrVIII 5218604 5220893 + ID = TGME49_270510; 2335 length = 2289 TGME49_chrXII 448136 451773 − ID = TGME49_307850; 2336 length = 3637 TGME49_chrXI 329830 333208 + ID = TGME49_308890; 2337 length = 3378 TGME49_chrVIIb 4982223 4984936 + ID = TGME49_255230; 2338 length = 2713 TGME49_chrVI 1338921 1340659 + ID = TGME49_240620; 2339 length = 1738 TGME49_chrVIIa 2710672 2712535 − ID = TGME49_203175; 2340 length = 1863 TGME49_chrIa 783634 786312 + ID = TGME49_294300; 2341 length = 2678 TGME49_chrVIIa 2207067 2211546 − ID = TGME49_203820; 2342 length = 4479 TGME49_chrVIIb 1410124 1411940 + ID = TGME49_262040; 2343 length = 1816 TGME49_chrV 1762123 1764217 − ID = TGME49_286620; 2344 length = 2094 TGME49_chrXI 2444171 2445480 − ID = TGME49_312120; 2345 length = 1309 TGME49_chrIX 2304200 2309017 + ID = TGME49_288030; 2346 length = 4817 TGME49_chrXII 3107046 3108961 + ID = TGME49_247020; 2347 length = 1915 TGME49_chrXII 1088408 1090747 − ID = TGME49_219190; 2348 length = 2339 TGME49_chrVIII 5243101 5244559 − ID = TGME49_270380; 2349 length = 1458 TGME49_chrIX 3661389 3662897 + ID = TGME49_290240; 2350 length = 1508 TGME49_chrIb 1465240 1466759 − ID = TGME49_209810; 2351 length = 1519 TGME49_chrVIIb 4093997 4097159 + ID = TGME49_257360; 2352 length = 3162 TGME49_chrIX 2730019 2732515 − ID = TGME49_288760; 2353 length = 2496 TGME49_chrXI 1804715 1808023 + ID = TGME49_311100; 2354 length = 3308 TGME49_chrX 4252113 4254822 − ID = TGME49_234250; 2355 length = 2709 TGME49_chrXI 3602353 3604400 − ID = TGME49_313677; 2356 length = 2047 TGME49_chrVIII 2912818 2914466 + ID = TGME49_233940; 2357 length = 1648 TGME49_chrX 7000639 7004503 + ID = TGME49_215530; 2358 length = 3864 TGME49_chrVIII 2289768 2291993 − ID = TGME49_232940; 2359 length = 2225 TGME49_chrX 5258198 5260065 − ID = TGME49_236060; 2360 length = 1867 TGME49_chrVIII 1884485 1889437 + ID = TGME49_232150; 2361 length = 4952 TGME49_chrXII 1882976 1885676 + ID = TGME49_217510; 2362 length = 2700 TGME49_chrX 1049905 1054351 − ID = TGME49_227280; 2363 length = 4446 TGME49_chrIa 1246263 1247746 − ID = TGME49_294880; 2364 length = 1483 TGME49_chrXII 5892198 5894986 − ID = TGME49_278770; 2365 length = 2788 TGME49_chrV 160407 162730 − ID = TGME49_220132; 2366 length = 2323 TGME49_chrX 3757076 3761771 + ID = TGME49_223520; 2367 length = 4695 TGME49_chrVIII 3809166 3812131 − ID = TGME49_272670; 2368 length = 2965 TGME49_chrVI 2816314 2820874 − ID = TGME49_243720; 2369 length = 4560 TGME49_chrX 1866919 1870597 + ID = TGME49_226010; 2370 length = 3678 TGME49_chrIa 1655906 1660726 + ID = TGME49_295640; 2371 length = 4820 TGME49_chrXII 2497045 2499685 + ID = TGME49_245730; 2372 length = 2640 TGME49_chrIb 1368907 1370576 + ID = TGME49_209640; 2373 length = 1669 TGME49_chrVIIa 1055163 1058273 − ID = TGME49_206340; 2374 length = 3110 TGME49_chrX 2106968 2108843 + ID = TGME49_225720; 2375 length = 1875 TGME49_chrVIIa 647552 651135 − ID = TGME49_304710; 2376 length = 3583 TGME49_chrVIIb 2433977 2435254 + ID = TGME49_260230; 2377 length = 1277 TGME49_chrVIII 5093749 5096679 + ID = TGME49_270660; 2378 length = 2930 TGME49_chrIX 4712512 4716695 + ID = TGME49_292375; 2379 length = 4183 TGME49_chrIX 3824648 3829311 + ID = TGME49_290670; 2380 length = 4663 TGME49_chrVIIa 2937184 2941974 + ID = TGME49_202930; 2381 length = 4790 TGME49_chrIb 264375 266961 + ID = TGME49_207760; 2382 length = 2586 TGME49_chrX 1064095 1066354 + ID = TGME49_227150; 2383 length = 2259 TGME49_chrVIIa 2238651 2240842 + ID = TGME49_203780; 2384 length = 2191 TGME49_chrXII 5511516 5514022 + ID = TGME49_251660; 2385 length = 2506 TGME49_chrIX 2729523 2732515 − ID = TGME49_288755; 2386 length = 2992 TGME49_chrXI 6523631 6524512 − ID = TGME49_215930; 2387 length = 881 TGME49_chrVIIa 1477054 1478405 + ID = TGME49_205310; 2388 length = 1351 TGME49_chrIa 1299896 1301681 + ID = TGME49_294980; 2389 length = 1785 TGME49_chrXII 5478826 5481198 + ID = TGME49_251600; 2390 length = 2372 TGME49_chrIX 195627 197977 + ID = TGME49_279410; 2391 length = 2350 TGME49_chrIX 2585255 2587746 − ID = TGME49_288500; 2392 length = 2491 TGME49_chrX 551024 553273 + ID = TGME49_228130; 2393 length = 2249 TGME49_chrVIII 1246299 1247749 − ID = TGME49_231110; 2394 length = 1450 TGME49_chrIX 6076772 6079949 + ID = TGME49_306440; 2395 length = 3177 TGME49_chrXI 112403 113739 + ID = TGME49_307030; 2396 length = 1336 TGME49_chrVIIa 1486724 1489206 − ID = TGME49_205300; 2397 length = 2482 TGME49_chrIX 3901723 3904302 + ID = TGME49_290870; 2398 length = 2579 TGME49_chrIX 3000871 3002525 − ID = TGME49_289110; 2399 length = 1654 TGME49_chrXII 6457403 6459638 − ID = TGME49_277880; 2400 length = 2235 TGME49_chrXI 1383113 1385121 − ID = TGME49_310490; 2401 length = 2008 TGME49_chrXII 3586775 3589201 + ID = TGME49_247790; 2402 length = 2426 TGME49_chrVI 2515479 2520512 − ID = TGME49_243290; 2403 length = 5033 TGME49_chrV 2197440 2199492 + ID = TGME49_285825; 2404 length = 2052 TGME49_chrVIIb 2639665 2642073 − ID = TGME49_259880; 2405 length = 2408 TGME49_chrIV 431416 433165 − ID = TGME49_320220; 2406 length = 1749 TGME49_chrX 5202475 5203919 + ID = TGME49_235960; 2407 length = 1444 TGME49_chrIa 1716758 1718720 − ID = TGME49_295590; 2408 length = 1962 TGME49_chrXI 5155486 5157169 − ID = TGME49_316140; 2409 length = 1683 TGME49_chrIX 3156705 3158620 + ID = TGME49_289300; 2410 length = 1915 TGME49_chrXI 1433031 1437316 − ID = TGME49_310530; 2411 length = 4285 TGME49_chrXII 6860302 6862811 + ID = TGME49_276900; 2412 length = 2509 TGME49_chrXI 4976219 4980235 + ID = TGME49_315780; 2413 length = 4016 TGME49_chrV 2340890 2344008 + ID = TGME49_285530; 2414 length = 3118 TGME49_chrIX 1539888 1543369 − ID = TGME49_265460; 2415 length = 3481 TGME49_chrX 447801 449204 + ID = TGME49_228250; 2416 length = 1403 TGME49_chrVI 3140054 3144151 + ID = TGME49_244260; 2417 length = 4097 TGME49_chrVIII 1584008 1588110 + ID = TGME49_231850; 2418 length = 4102 TGME49_chrXII 2862004 2863907 − ID = TGME49_246570; 2419 length = 1903 TGME49_chrXI 2664415 2666362 + ID = TGME49_312410; 2420 length = 1947 TGME49_chrVIIb 4219478 4221342 − ID = TGME49_257110; 2421 length = 1864 TGME49_chrVIIa 771238 775785 + ID = TGME49_206620; 2422 length = 4547 TGME49_chrII 1988671 1990219 + ID = TGME49_297780; 2423 length = 1548 TGME49_chrIX 2205860 2206820 + ID = TGME49_264468; 2424 length = 960 TGME49_chrVIIb 3575786 3577531 − ID = TGME49_258100; 2425 length = 1745 TGME49_chrIV 2324732 2325789 − ID = TGME49_301218; 2426 length = 1057 TGME49_chrXII 3033076 3037430 + ID = TGME49_246960; 2427 length = 4354 TGME49_chrXI 6360743 6365335 − ID = TGME49_216180; 2428 length = 4592 TGME49_chrVIIa 4364743 4368384 − ID = TGME49_282055; 2429 length = 3641 TGME49_chrVIII 4265575 4269776 + ID = TGME49_271950; 2430 length = 4201 TGME49_chrIX 327730 328648 − ID = TGME49_267830; 2431 length = 918 TGME49_chrII 1381881 1383797 − ID = TGME49_223040; 2432 length = 1916 TGME49_chrVIIb 3189128 3193873 − ID = TGME49_258780; 2433 length = 4745 TGME49_chrX 6602519 6604937 + ID = TGME49_214940; 2434 length = 2418 TGME49_chrXII 6221111 6222788 + ID = TGME49_278220; 2435 length = 1677 TGME49_chrIX 2394576 2396348 + ID = TGME49_288220; 2436 length = 1772 TGME49_chrXI 1696849 1700575 − ID = TGME49_310960; 2437 length = 3726 TGME49_chrX 1788172 1791138 + ID = TGME49_226110; 2438 length = 2966 TGME49_chrXI 2442282 2445480 − ID = TGME49_312110; 2439 length = 3198 TGME49_chrIX 219922 222865 + ID = TGME49_279370; 2440 length = 2943 TGME49_chrXI 4873358 4874729 − ID = TGME49_315650; 2441 length = 1371 TGME49_chrX 7446398 7448098 − ID = TGME49_207200; 2442 length = 1700 TGME49_chrV 2245097 2246666 − ID = TGME49_285780; 2443 length = 1569 TGME49_chrVIIa 515933 519026 + ID = TGME49_304480; 2444 length = 3093 TGME49_chrIb 1740080 1742565 + ID = TGME49_321540; 2445 length = 2485 TGME49_chrXI 4257933 4259598 + ID = TGME49_314740; 2446 length = 1665 TGME49_chrIb 761021 764259 + ID = TGME49_208540; 2447 length = 3238 TGME49_chrVI 3450966 3453208 − ID = TGME49_244680; 2448 length = 2242 TGME49_chrXI 4755042 4759341 − ID = TGME49_315490; 2449 length = 4299 TGME49_chrX 7372773 7375242 − ID = TGME49_207070; 2450 length = 2469 TGME49_chrXI 1587139 1588848 − ID = TGME49_310770; 2451 length = 1709 TGME49_chrVIII 943428 945265 − ID = TGME49_230660; 2452 length = 1837 TGME49_chrX 552123 553994 − ID = TGME49_228145; 2453 length = 1871 TGME49_chrIX 3459714 3462359 − ID = TGME49_289790; 2454 length = 2645 TGME49_chrVIIa 3339066 3342796 + ID = TGME49_202410; 2455 length = 3730 TGME49_chrXI 6491504 6494435 + ID = TGME49_215980; 2456 length = 2931 TGME49_chrXII 2583712 2585703 − ID = TGME49_245990; 2457 length = 1991 TGME49_chrVI 2637439 2640089 − ID = TGME49_243440; 2458 length = 2650 TGME49_chrV 2386130 2388506 + ID = TGME49_285480; 2459 length = 2376 TGME49_chrXII 3015620 3017791 − ID = TGME49_246910; 2460 length = 2171 TGME49_chrVIII 4302700 4305790 − ID = TGME49_271888; 2461 length = 3090 TGME49_chrVIIa 1866251 1869833 − ID = TGME49_204350; 2462 length = 3582 TGME49_chrX 5570013 5572759 − ID = TGME49_236910; 2463 length = 2746 TGME49_chrVIII 3179578 3181888 + ID = TGME49_273905; 2464 length = 2310 TGME49_chrX 6220314 6222244 − ID = TGME49_214295; 2465 length = 1930 TGME49_chrIX 2323164 2325191 − ID = TGME49_288040; 2466 length = 2027 TGME49_chrX 5603877 5606138 − ID = TGME49_236950; 2467 length = 2261 TGME49_chrVI 3027874 3028418 + ID = TGME49_244105; 2468 length = 544 TGME49_chrVIIb 2894337 2897600 − ID = TGME49_259200; 2469 length = 3263 TGME49_chrVIII 5588163 5592490 + ID = TGME49_269800; 2470 length = 4327 TGME49_chrX 2114298 2117359 + ID = TGME49_225690; 2471 length = 3061 TGME49_chrXII 4806777 4808523 + ID = TGME49_249810; 2472 length = 1746 TGME49_chrIX 199072 199671 + ID = TGME49_279405; 2473 length = 599 TGME49_chrX 2768326 2773227 − ID = TGME49_224860; 2474 length = 4901 TGME49_chrIa 1487388 1491082 − ID = TGME49_295920; 2475 length = 3694 TGME49_chrX 2226755 2227625 − ID = TGME49_225460; 2476 length = 870 TGME49_chrVIIa 4203574 4207561 − ID = TGME49_281575; 2477 length = 3987 TGME49_chrIX 5143608 5146410 + ID = TGME49_304990; 2478 length = 2802 TGME49_chrII 700644 704009 + ID = TGME49_221930; 2479 length = 3365 TGME49_chrVIII 4887753 4889510 + ID = TGME49_270900; 2480 length = 1757 TGME49_chrVIIb 238808 241001 − ID = TGME49_264010; 2481 length = 2193 TGME49_chrX 6494458 6497510 − ID = TGME49_214780; 2482 length = 3052 TGME49_chrX 3945025 3947454 + ID = TGME49_212275; 2483 length = 2429 TGME49_chrXI 784810 787257 + ID = TGME49_309752; 2484 length = 2447 TGME49_chrVIIb 654090 658976 + ID = TGME49_263280; 2485 length = 4886 TGME49_chrVI 1116533 1119178 + ID = TGME49_240255; 2486 length = 2645 TGME49_chrVIII 3232920 3235018 − ID = TGME49_273840; 2487 length = 2098 TGME49_chrX 4499729 4502574 + ID = TGME49_234622; 2488 length = 2845 TGME49_chrV 1439721 1442480 − ID = TGME49_213920; 2489 length = 2759 TGME49_chrVIIb 3409366 3413789 + ID = TGME49_258450; 2490 length = 4423 TGME49_chrVIIb 1424754 1426396 + ID = TGME49_262010; 2491 length = 1642 TGME49_chrIX 371574 373882 + ID = TGME49_267760; 2492 length = 2308 TGME49_chrVIII 5584328 5586338 + ID = TGME49_269830; 2493 length = 2010 TGME49_chrVI 465237 466979 + ID = TGME49_239110; 2494 length = 1742 TGME49_chrX 2669894 2671902 − ID = TGME49_224932; 2495 length = 2008 TGME49_chrVIIa 4422201 4425705 − ID = TGME49_282170; 2496 length = 3504 TGME49_chrXI 611994 614956 − ID = TGME49_309280; 2497 length = 2962 TGME49_chrIb 717976 721681 − ID = TGME49_208460; 2498 length = 3705 TGME49_chrXII 1423485 1426090 − ID = TGME49_218570; 2499 length = 2605 TGME49_chrXII 230042 234619 − ID = TGME49_300080; 2500 length = 4577 TGME49_chrXII 2457647 2459970 − ID = TGME49_245660; 2501 length = 2323 TGME49_chrVIII 6761552 6766520 − ID = TGME49_200250; 2502 length = 4968 TGME49_chrXII 2287999 2289797 − ID = TGME49_245460; 2503 length = 1798 TGME49_chrXII 3767325 3771010 + ID = TGME49_248270; 2504 length = 3685 TGME49_chrVIIb 4267062 4268545 + ID = TGME49_257040; 2505 length = 1483 TGME49_chrXI 5739747 5741353 + ID = TGME49_216980; 2506 length = 1606 TGME49_chrVIIa 3566006 3567436 + ID = TGME49_202160; 2507 length = 1430 TGME49_chrVIII 321618 326501 + ID = TGME49_229630; 2508 length = 4883 TGME49_chrXI 4518461 4520837 − ID = TGME49_315140; 2509 length = 2376 TGME49_chrX 5949504 5953689 + ID = TGME49_237530; 2510 length = 4185 TGME49_chrX 3780406 3782419 + ID = TGME49_223490; 2511 length = 2013 TGME49_chrII 1156231 1160734 + ID = TGME49_222660; 2512 length = 4503 TGME49_chrVI 2851748 2852954 − ID = TGME49_243770; 2513 length = 1206 TGME49_chrVI 539374 541507 + ID = TGME49_239310; 2514 length = 2133 TGME49_chrXII 2997764 3002544 − ID = TGME49_246780; 2515 length = 4780 TGME49_chrXII 849594 852277 − ID = TGME49_219570; 2516 length = 2683 TGME49_chrX 2240720 2242446 + ID = TGME49_225435; 2517 length = 1726 TGME49_chrVIII 2005504 2007905 − ID = TGME49_232310; 2518 length = 2401 TGME49_chrVIIb 82870 85185 − ID = TGME49_264210; 2519 length = 2315 TGME49_chrII 267810 272793 + ID = TGME49_221340; 2520 length = 4983 TGME49_chrV 2468810 2471121 + ID = TGME49_285268; 2521 length = 2311 TGME49_chrIX 2445296 2446946 − ID = TGME49_288320; 2522 length = 1650 TGME49_chrVIIa 133327 135436 − ID = TGME49_280740; 2523 length = 2109 TGME49_chrIb 864047 867064 − ID = TGME49_208790; 2524 length = 3017 TGME49_chrX 6764674 6769143 + ID = TGME49_215130; 2525 length = 4469 TGME49_chrX 2306330 2309400 − ID = TGME49_225340; 2526 length = 3070 TGME49_chrVIII 3300013 3302035 − ID = TGME49_273740; 2527 length = 2022 TGME49_chrIX 2102213 2103786 + ID = TGME49_264700; 2528 length = 1573 TGME49_chrXI 288223 289585 − ID = TGME49_308820; 2529 length = 1362 TGME49_chrX 7191885 7195726 − ID = TGME49_275340; 2530 length = 3841 TGME49_chrIX 3487672 3492693 − ID = TGME49_289850; 2531 length = 5021 TGME49_chrX 7028124 7032199 − ID = TGME49_215570; 2532 length = 4075 TGME49_chrVIIa 2186716 2190767 + ID = TGME49_203830; 2533 length = 4051 TGME49_chrVIII 4251639 4253470 − ID = TGME49_271980; 2534 length = 1831 TGME49_chrIb 1643069 1646070 − ID = TGME49_321680; 2535 length = 3001 TGME49_chrIX 5602450 5604206 + ID = TGME49_305820; 2536 length = 1756 TGME49_chrVIII 2991968 2993305 − ID = TGME49_274140; 2537 length = 1337 TGME49_chrVIII 5299297 5301755 − ID = TGME49_270273; 2538 length = 2458 TGME49_chrX 2150245 2152288 − ID = TGME49_225570; 2539 length = 2043 TGME49_chrVI 394289 399092 − ID = TGME49_239010; 2540 length = 4803 TGME49_chrV 1875620 1880133 − ID = TGME49_286270; 2541 length = 4513 TGME49_chrXI 1366381 1368421 − ID = TGME49_310455; 2542 length = 2040 TGME49_chrXII 4113710 4117497 + ID = TGME49_248720; 2543 length = 3787 TGME49_chrXII 2653676 2656148 − ID = TGME49_246080; 2544 length = 2472 TGME49_chrV 1349479 1353386 − ID = TGME49_213810; 2545 length = 3907 TGME49_chrVIIa 2290516 2292314 + ID = TGME49_203720; 2546 length = 1798 TGME49_chrIV 1101627 1104332 − ID = TGME49_318770; 2547 length = 2705 TGME49_chrVIIb 428872 432171 + ID = TGME49_263610; 2548 length = 3299 TGME49_chrIX 6094343 6098588 − ID = TGME49_306450; 2549 length = 4245 TGME49_chrVIIa 945669 947912 − ID = TGME49_206480; 2550 length = 2243 TGME49_chrVI 1061389 1062893 + ID = TGME49_240200; 2551 length = 1504 TGME49_chrX 5276493 5278337 − ID = TGME49_236080; 2552 length = 1844 TGME49_chrIX 4400803 4405615 + ID = TGME49_291930; 2553 length = 4812 TGME49_chrIV 1830458 1834833 + ID = TGME49_211310; 2554 length = 4375 TGME49_chrIV 800777 803054 + ID = TGME49_319658; 2555 length = 2277 TGME49_chrII 355915 357775 − ID = TGME49_221440; 2556 length = 1860 TGME49_chrXI 1857706 1859770 − ID = TGME49_311200; 2557 length = 2064 TGME49_chrIV 173575 175464 + ID = TGME49_320640; 2558 length = 1889 TGME49_chrIX 4981120 4983371 − ID = TGME49_307575; 2559 length = 2251 TGME49_chrII 1514515 1516458 − ID = TGME49_297060; 2560 length = 1943 TGME49_chrVIIa 3755368 3756835 + ID = TGME49_201830; 2561 length = 1467 TGME49_chrVI 1484701 1486911 − ID = TGME49_240860; 2562 length = 2210 TGME49_chrXI 451688 453382 − ID = TGME49_309030; 2563 length = 1694 TGME49_chrVIIb 655477 659865 − ID = TGME49_263290; 2564 length = 4388 TGME49_chrX 309061 310991 + ID = TGME49_228440; 2565 length = 1930 TGME49_chrVIIa 4363284 4367705 + ID = TGME49_282070; 2566 length = 4421 TGME49_chrX 3399177 3401893 − ID = TGME49_224000; 2567 length = 2716 TGME49_chrIX 3110902 3114645 − ID = TGME49_289240; 2568 length = 3743 TGME49_chrX 7149209 7152824 + ID = TGME49_215775; 2569 length = 3615 TGME49_chrIV 566220 568593 + ID = TGME49_320030; 2570 length = 2373 TGME49_chrVIII 4360273 4363025 − ID = TGME49_271800; 2571 length = 2752 TGME49_chrXII 2149793 2150458 − ID = TGME49_217810; 2572 length = 665 TGME49_chrX 1677412 1680531 + ID = TGME49_226370; 2573 length = 3119 TGME49_chrIX 2009537 2012433 − ID = TGME49_264805; 2574 length = 2896 TGME49_chrXII 898597 901257 + ID = TGME49_219500; 2575 length = 2660 TGME49_chrVIII 5068704 5071169 − ID = TGME49_270700; 2576 length = 2465 TGME49_chrVIIa 2027671 2030677 + ID = TGME49_204050; 2577 length = 3006 TGME49_chrVIII 1649426 1651273 − ID = TGME49_231920; 2578 length = 1847 TGME49_chrXII 5008120 5009885 + ID = TGME49_250060; 2579 length = 1765 TGME49_chrVIII 388039 391218 − ID = TGME49_229690; 2580 length = 3179 TGME49_chrIX 2452386 2456727 + ID = TGME49_288340; 2581 length = 4341 TGME49_chrVIII 3821895 3824021 − ID = TGME49_272645; 2582 length = 2126 TGME49_chrXI 1390231 1391395 + ID = TGME49_310515; 2583 length = 1164 TGME49_chrXI 1151478 1152895 − ID = TGME49_310200; 2584 length = 1417 TGME49_chrVI 3450042 3452022 + ID = TGME49_244690; 2585 length = 1980 TGME49_chrVI 8252 9653 + ID = TGME49_238010; 2586 length = 1401 TGME49_chrVIIa 1054453 1057137 + ID = TGME49_206330; 2587 length = 2684 TGME49_chrVIIb 3985832 3987219 + ID = TGME49_257540; 2588 length = 1387 TGME49_chrIX 797312 799366 − ID = TGME49_267070; 2589 length = 2054 TGME49_chrVIIa 3113269 3117191 + ID = TGME49_202670; 2590 length = 3922 TGME49_chrIX 1108922 1111021 − ID = TGME49_266480; 2591 length = 2099 TGME49_chrVIII 6007557 6009244 − ID = TGME49_269190; 2592 length = 1687 TGME49_chrII 1888623 1893021 − ID = TGME49_297647; 2593 length = 4398 TGME49_chrV 871531 873751 − ID = TGME49_213240; 2594 length = 2220 TGME49_chrVIII 63466 67252 + ID = TGME49_229170; 2595 length = 3786 TGME49_chrV 1777822 1780056 + ID = TGME49_286570; 2596 length = 2234 TGME49_chrX 2225100 2226843 + ID = TGME49_225450; 2597 length = 1743 TGME49_chrVIII 561740 564177 − ID = TGME49_230030; 2598 length = 2437 TGME49_chrX 1938993 1940952 + ID = TGME49_225910; 2599 length = 1959 TGME49_chrIb 471344 476049 + ID = TGME49_207965; 2600 length = 4705 TGME49_chrIX 4978916 4982404 + ID = TGME49_307580; 2601 length = 3488 TGME49_chrVIIa 160728 162946 − ID = TGME49_280710; 2602 length = 2218 TGME49_chrVIIa 275203 280157 + ID = TGME49_280590; 2603 length = 4954 TGME49_chrVIIb 858403 859587 + ID = TGME49_263030; 2604 length = 1184 TGME49_chrVIII 6600438 6602216 + ID = TGME49_268250; 2605 length = 1778 TGME49_chrVIIa 4395894 4398590 + ID = TGME49_282140; 2606 length = 2696 TGME49_chrIa 192097 195881 + ID = TGME49_293250; 2607 length = 3784 TGME49_chrV 2252900 2254312 + ID = TGME49_285750; 2608 length = 1412 TGME49_chrXI 1317160 1319239 + ID = TGME49_310400; 2609 length = 2079 TGME49_chrVIII 1664718 1667016 + ID = TGME49_231950; 2610 length = 2298 TGME49_chrIX 2899729 2901760 − ID = TGME49_288990; 2611 length = 2031 TGME49_chrX 6972539 6973901 + ID = TGME49_215470; 2612 length = 1362 TGME49_chrIX 4396776 4400328 − ID = TGME49_291890; 2613 length = 3552 TGME49_chrIX 772170 775776 − ID = TGME49_267120; 2614 length = 3606 TGME49_chrXI 1110455 1114100 + ID = TGME49_310173; 2615 length = 3645 TGME49_chrXII 5711051 5713503 − ID = TGME49_278990; 2616 length = 2452 TGME49_chrIV 1118559 1122425 − ID = TGME49_318730; 2617 length = 3866 TGME49_chrVIIa 1259192 1261805 − ID = TGME49_205625; 2618 length = 2613 TGME49_chrX 6941543 6942949 − ID = TGME49_215390; 2619 length = 1406 TGME49_chrX 4385644 4390371 + ID = TGME49_234440; 2620 length = 4727 TGME49_chrX 4525519 4528145 + ID = TGME49_234690; 2621 length = 2626 TGME49_chrXI 3917090 3919270 − ID = TGME49_314090; 2622 length = 2180 TGME49_chrXI 6370740 6375773 + ID = TGME49_216155; 2623 length = 5033 TGME49_chrV 1925673 1927982 − ID = TGME49_286200; 2624 length = 2309 TGME49_chrXII 6381841 6386433 + ID = TGME49_277950; 2625 length = 4592 TGME49_chrX 804068 805942 + ID = TGME49_227810; 2626 length = 1874 TGME49_chrVIIb 4668460 4670573 + ID = TGME49_255870; 2627 length = 2113 TGME49_chrVIII 2292223 2295223 + ID = TGME49_232960; 2628 length = 3000 TGME49_chrVIII 5310860 5313259 − ID = TGME49_270250; 2629 length = 2399 TGME49_chrXII 802072 803527 + ID = TGME49_219630; 2630 length = 1455 TGME49_chrVIII 4546700 4548626 + ID = TGME49_271360; 2631 length = 1926 TGME49_chrXI 599056 600665 + ID = TGME49_309265; 2632 length = 1609 TGME49_chrVIII 3924549 3926856 − ID = TGME49_272530; 2633 length = 2307 TGME49_chrXI 1255766 1257660 − ID = TGME49_310310; 2634 length = 1894 TGME49_chrVIIb 2762832 2764576 − ID = TGME49_259590; 2635 length = 1744 TGME49_chrX 2456056 2459220 − ID = TGME49_225140; 2636 length = 3164 TGME49_chrVIII 5775921 5778051 + ID = TGME49_269460; 2637 length = 2130 TGME49_chrVI 3016532 3018964 − ID = TGME49_244090; 2638 length = 2432 TGME49_chrVIIa 1677841 1681517 + ID = TGME49_205000; 2639 length = 3676 TGME49_chrXI 3582351 3585505 − ID = TGME49_313650; 2640 length = 3154 TGME49_chrII 1271109 1273811 − ID = TGME49_222860; 2641 length = 2702 TGME49_chrXII 577408 579217 − ID = TGME49_308096; 2642 length = 1809 TGME49_chrXII 3175514 3177639 − ID = TGME49_247195; 2643 length = 2125 TGME49_chrVIIa 2571840 2574320 − ID = TGME49_203330; 2644 length = 2480 TGME49_chrVIIa 2523240 2527928 + ID = TGME49_203380; 2645 length = 4688 TGME49_chrIV 1941441 1942608 + ID = TGME49_211080; 2646 length = 1167 TGME49_chrXII 6089434 6093280 − ID = TGME49_278460; 2647 length = 3846 TGME49_chrXII 6081058 6083036 − ID = TGME49_278490; 2648 length = 1978 TGME49_chrXII 2941137 2943790 + ID = TGME49_246720; 2649 length = 2653 TGME49_chrVI 3196293 3199662 − ID = TGME49_244335; 2650 length = 3369 TGME49_chrVIIb 1031571 1036168 − ID = TGME49_262780; 2651 length = 4597 TGME49_chrVI 1303181 1305102 − ID = TGME49_240510; 2652 length = 1921 TGME49_chrIV 2021658 2023438 − ID = TGME49_210840; 2653 length = 1780 TGME49_chrVIII 3226422 3228068 − ID = TGME49_273850; 2654 length = 1646 TGME49_chrVIIb 3101472 3103925 − ID = TGME49_258900; 2655 length = 2453 TGME49_chrXI 1160835 1164143 + ID = TGME49_310220; 2656 length = 3308 TGME49_chrXI 551152 552779 + ID = TGME49_309195; 2657 length = 1627 TGME49_chrXI 2837821 2840040 − ID = TGME49_312622; 2658 length = 2219 TGME49_chrII 1387041 1390571 + ID = TGME49_223060; 2659 length = 3530 TGME49_chrIV 1941441 1943297 + ID = TGME49_211070; 2660 length = 1856 TGME49_chrXI 785847 788515 − ID = TGME49_309740; 2661 length = 2668 TGME49_chrX 3052243 3054585 − ID = TGME49_224470; 2662 length = 2342 TGME49_chrIX 4277659 4279338 − ID = TGME49_291370; 2663 length = 1679 TGME49_chrXI 826261 828335 − ID = TGME49_309800; 2664 length = 2074 TGME49_chrXII 6840262 6842703 + ID = TGME49_276930; 2665 length = 2441 TGME49_chrIV 346077 348428 − ID = TGME49_320450; 2666 length = 2351 TGME49_chrXII 1649988 1651365 − ID = TGME49_218250; 2667 length = 1377 TGME49_chrXII 5151010 5152773 + ID = TGME49_250730; 2668 length = 1763 TGME49_chrX 4002470 4005528 + ID = TGME49_212160; 2669 length = 3058 TGME49_chrVIIb 2126932 2129789 + ID = TGME49_260600; 2670 length = 2857 TGME49_chrXI 4406805 4410963 − ID = TGME49_314910; 2671 length = 4158 TGME49_chrVIII 6257556 6259358 + ID = TGME49_268835; 2672 length = 1802 TGME49_chrXII 1875381 1876656 + ID = TGME49_217490; 2673 length = 1275 TGME49_chrIX 3856756 3857919 − ID = TGME49_290710; 2674 length = 1163 TGME49_chrVIII 470060 474349 + ID = TGME49_229930; 2675 length = 4289 TGME49_chrXI 4025920 4030724 + ID = TGME49_314358; 2676 length = 4804 TGME49_chrIb 460087 461835 − ID = TGME49_207955; 2677 length = 1748 TGME49_chrVIIa 2490731 2493062 − ID = TGME49_203480; 2678 length = 2331 TGME49_chrII 562040 565277 + ID = TGME49_221685; 2679 length = 3237 TGME49_chrV 2462151 2465375 − ID = TGME49_285290; 2680 length = 3224 TGME49_chrV 645279 647282 + ID = TGME49_212850; 2681 length = 2003 TGME49_chrVIII 5331414 5333301 + ID = TGME49_270210; 2682 length = 1887 TGME49_chrVIIb 912343 914333 − ID = TGME49_262935; 2683 length = 1990 TGME49_chrVIIa 4126871 4128947 + ID = TGME49_281450; 2684 length = 2076 TGME49_chrVI 2158909 2160846 + ID = TGME49_242650; 2685 length = 1937 TGME49_chrVIIb 4129894 4131374 − ID = TGME49_257330; 2686 length = 1480 TGME49_chrXII 1555009 1560065 − ID = TGME49_218380; 2687 length = 5056 TGME49_chrXII 3798058 3802342 − ID = TGME49_248300; 2688 length = 4284 TGME49_chrX 2773657 2776323 + ID = TGME49_224850; 2689 length = 2666 TGME49_chrXII 859876 861462 − ID = TGME49_219550; 2690 length = 1586 TGME49_chrVIIb 3133820 3137682 + ID = TGME49_258840; 2691 length = 3862 TGME49_chrIX 4560778 4562922 + ID = TGME49_292120; 2692 length = 2144 TGME49_chrIX 1317799 1319959 + ID = TGME49_266070; 2693 length = 2160 TGME49_chrVIIa 58368 61406 − ID = TGME49_280810; 2694 length = 3038 TGME49_chrVIII 6365189 6366539 − ID = TGME49_268690; 2695 length = 1350 TGME49_chrXI 6058978 6060618 − ID = TGME49_216600; 2696 length = 1640 TGME49_chrVI 1334799 1336826 − ID = TGME49_240590; 2697 length = 2027 TGME49_chrV 1973489 1975650 − ID = TGME49_286130; 2698 length = 2161 TGME49_chrVIIb 1101193 1106043 − ID = TGME49_262655; 2699 length = 4850 TGME49_chrII 403605 405254 + ID = TGME49_221510; 2700 length = 1649 TGME49_chrIV 1735322 1737748 − ID = TGME49_211420; 2701 length = 2426 TGME49_chrVIII 4650985 4654271 + ID = TGME49_271182; 2702 length = 3286 TGME49_chrVIIb 921322 925018 − ID = TGME49_262930; 2703 length = 3696 TGME49_chrVI 2311797 2313889 − ID = TGME49_242800; 2704 length = 2092 TGME49_chrIX 4820131 4821972 + ID = TGME49_210390; 2705 length = 1841 TGME49_chrII 1626675 1629738 − ID = TGME49_297220; 2706 length = 3063 TGME49_chrXII 3445460 3450482 + ID = TGME49_247630; 2707 length = 5022 TGME49_chrX 4800098 4801840 − ID = TGME49_235350; 2708 length = 1742 TGME49_chrVIII 651925 653885 − ID = TGME49_230160; 2709 length = 1960 TGME49_chrVIII 6674933 6676585 + ID = TGME49_268035; 2710 length = 1652 TGME49_chrXI 26464 30284 − ID = TGME49_307260; 2711 length = 3820 TGME49_chrVI 3115170 3117323 − ID = TGME49_244200; 2712 length = 2153 TGME49_chrXII 899075 901898 − ID = TGME49_219510; 2713 length = 2823 TGME49_chrX 7169371 7172828 + ID = TGME49_275320; 2714 length = 3457 TGME49_chrXII 2953442 2955259 + ID = TGME49_246740; 2715 length = 1817 TGME49_chrIa 1445468 1449325 + ID = TGME49_295990; 2716 length = 3857 TGME49_chrVIIb 4614055 4617990 + ID = TGME49_255940; 2717 length = 3935 TGME49_chrIb 1471673 1474994 − ID = TGME49_209820; 2718 length = 3321 TGME49_chrVI 918303 921331 + ID = TGME49_239795; 2719 length = 3028 TGME49_chrVIIa 1343739 1346394 + ID = TGME49_205540; 2720 length = 2655 TGME49_chrXI 3259153 3260521 − ID = TGME49_313305; 2721 length = 1368 TGME49_chrIX 5461619 5466485 + ID = TGME49_305560; 2722 length = 4866 TGME49_chrV 2997437 2999458 + ID = TGME49_283740; 2723 length = 2021 TGME49_chrIX 4903736 4907468 + ID = TGME49_210270; 2724 length = 3732 TGME49_chrVIIa 3323217 3327698 − ID = TGME49_202450; 2725 length = 4481 TGME49_chrX 5306045 5306976 + ID = TGME49_236153; 2726 length = 931 TGME49_chrIV 1166825 1168908 + ID = TGME49_318650; 2727 length = 2083 TGME49_chrVIIb 982149 984168 − ID = TGME49_262840; 2728 length = 2019 TGME49_chrIX 5435334 5438062 + ID = TGME49_305490; 2729 length = 2728 TGME49_chrXI 2989152 2990445 − ID = TGME49_312930; 2730 length = 1293 TGME49_chrIX 3632418 3634414 − ID = TGME49_290180; 2731 length = 1996 TGME49_chrVIIa 1843982 1846698 − ID = TGME49_204380; 2732 length = 2716 TGME49_chrVIII 1887186 1890535 − ID = TGME49_232140; 2733 length = 3349 TGME49_chrIV 823132 825847 − ID = TGME49_319630; 2734 length = 2715 TGME49_chrVI 2636729 2639733 + ID = TGME49_243450; 2735 length = 3004 TGME49_chrX 3856731 3858953 + ID = TGME49_223410; 2736 length = 2222 TGME49_chrXII 4678421 4682858 − ID = TGME49_249600; 2737 length = 4437 TGME49_chrXI 4509922 4511567 − ID = TGME49_315130; 2738 length = 1645 TGME49_chrIa 1153066 1154657 + ID = TGME49_294812; 2739 length = 1591 TGME49_chrIX 706165 708319 − ID = TGME49_267350; 2740 length = 2154 TGME49_chrXII 4392567 4397271 + ID = TGME49_249250; 2741 length = 4704 TGME49_chrVIII 3620478 3622646 + ID = TGME49_273200; 2742 length = 2168 TGME49_chrIX 3048775 3052445 − ID = TGME49_289180; 2743 length = 3670 TGME49_chrX 5786435 5789375 + ID = TGME49_237220; 2744 length = 2940 TGME49_chrX 3448596 3453595 + ID = TGME49_223920; 2745 length = 4999 TGME49_chrVI 1618811 1622040 + ID = TGME49_241010; 2746 length = 3229 TGME49_chrXII 2808694 2813152 − ID = TGME49_246500; 2747 length = 4458 TGME49_chrIX 952354 954209 − ID = TGME49_266820; 2748 length = 1855 TGME49_chrX 152090 154165 − ID = TGME49_228770; 2749 length = 2075 TGME49_chrXII 3243448 3245120 + ID = TGME49_247305; 2750 length = 1672 TGME49_chrX 1028684 1030566 − ID = TGME49_227320; 2751 length = 1882 TGME49_chrVI 453972 456175 + ID = TGME49_239087; 2752 length = 2203 TGME49_chrVIII 370373 371876 + ID = TGME49_229670; 2753 length = 1503 TGME49_chrXII 2205095 2207381 − ID = TGME49_217890; 2754 length = 2286 TGME49_chrVIII 1171719 1176344 + ID = TGME49_230990; 2755 length = 4625 TGME49_chrX 6719697 6721912 − ID = TGME49_215040; 2756 length = 2215 TGME49_chrXII 3623594 3625340 − ID = TGME49_247920; 2757 length = 1746 TGME49_chrIX 5921208 5925102 − ID = TGME49_306290; 2758 length = 3894 TGME49_chrVIIb 945683 947561 + ID = TGME49_262890; 2759 length = 1878 TGME49_chrVIII 3793351 3798091 − ID = TGME49_272695; 2760 length = 4740 TGME49_chrVIIb 283563 284791 − ID = TGME49_263870; 2761 length = 1228 TGME49_chrXI 2898675 2900997 + ID = TGME49_312680; 2762 length = 2322 TGME49_chrXI 4269493 4271271 + ID = TGME49_314760; 2763 length = 1778 TGME49_chrIV 743496 746016 − ID = TGME49_319860; 2764 length = 2520 TGME49_chrXII 5944752 5946781 − ID = TGME49_278670; 2765 length = 2029 TGME49_chrVIIb 329609 331237 + ID = TGME49_263760; 2766 length = 1628 TGME49_chrVIIb 3612696 3614760 − ID = TGME49_258070; 2767 length = 2064 TGME49_chrII 446960 451815 + ID = TGME49_221580; 2768 length = 4855 TGME49_chrXII 5142000 5143982 + ID = TGME49_250710; 2769 length = 1982 TGME49_chrVIIa 348808 351228 − ID = TGME49_280500; 2770 length = 2420 TGME49_chrXII 1626315 1628343 + ID = TGME49_218280; 2771 length = 2028 TGME49_chrVIII 4982170 4987009 − ID = TGME49_270810; 2772 length = 4839 TGME49_chrXI 5211986 5213771 − ID = TGME49_316250; 2773 length = 1785 TGME49_chrVIIa 1419599 1424205 + ID = TGME49_205398; 2774 length = 4606 TGME49_chrXII 736337 738273 + ID = TGME49_219678; 2775 length = 1936 TGME49_chrXII 1969472 1971512 − ID = TGME49_217640; 2776 length = 2040 TGME49_chrX 2158857 2163020 − ID = TGME49_225560; 2777 length = 4163 TGME49_chrV 1527084 1529358 − ID = TGME49_287210; 2778 length = 2274 TGME49_chrXII 2985681 2987023 − ID = TGME49_246763; 2779 length = 1342 TGME49_chrIV 1188460 1192145 + ID = TGME49_318610; 2780 length = 3685 TGME49_chrVIIb 3118623 3122518 − ID = TGME49_258870; 2781 length = 3895 TGME49_chrVIII 4338895 4340907 + ID = TGME49_271830; 2782 length = 2012 TGME49_chrXI 120398 121691 + ID = TGME49_307015; 2783 length = 1293 TGME49_chrVIIb 4652230 4655422 + ID = TGME49_255880; 2784 length = 3192 TGME49_chrVIII 2229753 2232098 − ID = TGME49_232680; 2785 length = 2345 TGME49_chrXII 3201946 3205868 − ID = TGME49_247250; 2786 length = 3922 TGME49_chrVIII 1995325 1996498 + ID = TGME49_232290; 2787 length = 1173 TGME49_chrXII 2349495 2351982 + ID = TGME49_245530; 2788 length = 2487 TGME49_chrVIII 5296820 5298844 − ID = TGME49_270277; 2789 length = 2024 TGME49_chrXII 6474091 6476198 − ID = TGME49_277860; 2790 length = 2107 TGME49_chrXI 1331785 1333925 − ID = TGME49_310420; 2791 length = 2140 TGME49_chrX 6606599 6611152 + ID = TGME49_214950; 2792 length = 4553 TGME49_chrIb 1838024 1840558 + ID = TGME49_321400; 2793 length = 2534 TGME49_chrX 1867675 1871933 − ID = TGME49_226020; 2794 length = 4258 TGME49_chrVIII 6812170 6815991 + ID = TGME49_200350; 2795 length = 3821 TGME49_chrXII 4797395 4799343 − ID = TGME49_249780; 2796 length = 1948 TGME49_chrVIII 5106894 5110114 + ID = TGME49_270640; 2797 length = 3220 TGME49_chrXI 1856929 1859770 − ID = TGME49_311190; 2798 length = 2841 TGME49_chrVIIa 3429130 3430859 − ID = TGME49_202320; 2799 length = 1729 TGME49_chrVIIb 181366 185076 + ID = TGME49_264100; 2800 length = 3710 TGME49_chrVIIb 3646582 3648630 − ID = TGME49_258020; 2801 length = 2048 TGME49_chrV 2798448 2800018 + ID = TGME49_284160; 2802 length = 1570 TGME49_chrXII 5430181 5431564 + ID = TGME49_251500; 2803 length = 1383 TGME49_chrIa 684229 685834 + ID = TGME49_294190; 2804 length = 1605 TGME49_chrX 4514799 4517679 + ID = TGME49_234670; 2805 length = 2880 TGME49_chrIb 19922 22201 − ID = TGME49_207380; 2806 length = 2279 TGME49_chrXII 2837852 2840190 + ID = TGME49_246540; 2807 length = 2338 TGME49_chrVIIa 3259896 3262598 + ID = TGME49_202520; 2808 length = 2702 TGME49_chrXI 2665525 2666765 − ID = TGME49_312400; 2809 length = 1240 TGME49_chrII 355180 357222 + ID = TGME49_221450; 2810 length = 2042 TGME49_chrX 2433230 2435647 + ID = TGME49_225190; 2811 length = 2417 TGME49_chrVIII 57748 60111 − ID = TGME49_229150; 2812 length = 2363 TGME49_chrVIIb 4885643 4888514 + ID = TGME49_255340; 2813 length = 2871 TGME49_chrV 725744 726888 + ID = TGME49_212955; 2814 length = 1144 TGME49_chrVI 1580744 1581416 − ID = TGME49_240940; 2815 length = 672 TGME49_chrVIII 928298 930205 − ID = TGME49_230640; 2816 length = 1907 TGME49_chrXII 2832742 2834747 + ID = TGME49_246530; 2817 length = 2005 TGME49_chrVIII 56761 59366 + ID = TGME49_229160; 2818 length = 2605 TGME49_chrIX 3666729 3669016 + ID = TGME49_290260; 2819 length = 2287 TGME49_chrVIII 6374094 6376344 − ID = TGME49_268660; 2820 length = 2250 TGME49_chrIV 1692110 1694217 − ID = TGME49_211480; 2821 length = 2107 TGME49_chrVIIb 2272974 2275367 − ID = TGME49_260440; 2822 length = 2393 TGME49_chrVIII 4880298 4882600 + ID = TGME49_270910; 2823 length = 2302 TGME49_chrXII 985332 987309 + ID = TGME49_219300; 2824 length = 1977 TGME49_chrX 5430041 5431958 + ID = TGME49_236570; 2825 length = 1917 TGME49_chrVIIa 1847823 1850467 + ID = TGME49_204360; 2826 length = 2644 TGME49_chrXII 3743680 3747903 + ID = TGME49_248225; 2827 length = 4223 TGME49_chrX 3783781 3785405 + ID = TGME49_223485; 2828 length = 1624 TGME49_chrXI 4270243 4271815 − ID = TGME49_314750; 2829 length = 1572 TGME49_chrX 1078543 1080826 + ID = TGME49_227115; 2830 length = 2283 TGME49_chrXII 4659619 4662247 − ID = TGME49_249575; 2831 length = 2628 TGME49_chrVIIb 2023964 2026656 − ID = TGME49_260825; 2832 length = 2692 TGME49_chrIX 4639418 4641832 + ID = TGME49_292245; 2833 length = 2414 TGME49_chrVIII 5798086 5801508 + ID = TGME49_269430; 2834 length = 3422 TGME49_chrX 5080892 5083213 − ID = TGME49_235730; 2835 length = 2321 TGME49_chrIX 283315 284597 − ID = TGME49_279310; 2836 length = 1282 TGME49_chrXII 919752 924441 − ID = TGME49_219485; 2837 length = 4689 TGME49_chrIX 2544921 2548040 + ID = TGME49_288450; 2838 length = 3119 TGME49_chrXI 5343323 5345659 − ID = TGME49_316480; 2839 length = 2336 TGME49_chrVI 207532 210236 + ID = TGME49_238410; 2840 length = 2704 TGME49_chrXI 216523 218588 + ID = TGME49_306880; 2841 length = 2065 TGME49_chrXI 513332 516847 + ID = TGME49_309130; 2842 length = 3515 TGME49_chrIX 5351945 5353735 − ID = TGME49_305310; 2843 length = 1790 TGME49_chrIX 1260940 1263377 + ID = TGME49_266260; 2844 length = 2437 TGME49_chrVIII 6773085 6775554 + ID = TGME49_200290; 2845 length = 2469 TGME49_chrII 1859313 1862244 − ID = TGME49_297520; 2846 length = 2931 TGME49_chrVIIb 4221737 4224344 + ID = TGME49_257090; 2847 length = 2607 TGME49_chrVIII 2074694 2076558 − ID = TGME49_232400; 2848 length = 1864 TGME49_chrX 5184565 5187267 − ID = TGME49_235920; 2849 length = 2702 TGME49_chrVIIb 3862212 3863945 + ID = TGME49_257730; 2850 length = 1733 TGME49_chrIX 3935623 3938663 + ID = TGME49_290920; 2851 length = 3040 TGME49_chrIb 609246 611891 + ID = TGME49_208330; 2852 length = 2645 TGME49_chrX 5569094 5572139 + ID = TGME49_236920; 2853 length = 3045 TGME49_chrVIIb 4551227 4555100 − ID = TGME49_256040; 2854 length = 3873 TGME49_chrX 753755 755679 − ID = TGME49_227890; 2855 length = 1924 TGME49_chrVI 686164 689115 − ID = TGME49_239475; 2856 length = 2951 TGME49_chrXI 3941340 3945803 + ID = TGME49_314240; 2857 length = 4463 TGME49_chrVIIb 3175832 3180410 − ID = TGME49_258810; 2858 length = 4578 TGME49_chrVIII 4081769 4082967 + ID = TGME49_272300; 2859 length = 1198 TGME49_chrVIIb 1535057 1538674 − ID = TGME49_261780; 2860 length = 3617 TGME49_chrXI 3345412 3347300 − ID = TGME49_313400; 2861 length = 1888 TGME49_chrVIII 2239078 2241114 + ID = TGME49_232730; 2862 length = 2036 TGME49_chrX 3985430 3987663 + ID = TGME49_212190; 2863 length = 2233 TGME49_chrXII 6261861 6263784 + ID = TGME49_278160; 2864 length = 1923 TGME49_chrX 1134133 1136564 + ID = TGME49_227015; 2865 length = 2431 TGME49_chrIX 4927380 4929331 − ID = TGME49_210255; 2866 length = 1951 TGME49_chrVIII 494173 497365 − ID = TGME49_229970; 2867 length = 3192 TGME49_chrXI 4603674 4605166 − ID = TGME49_315250; 2868 length = 1492 TGME49_chrVIIa 385701 390631 − ID = TGME49_280465; 2869 length = 4930 TGME49_chrXI 5186674 5188422 + ID = TGME49_316210; 2870 length = 1748 TGME49_chrVIII 2721138 2725943 − ID = TGME49_233610; 2871 length = 4805 TGME49_chrX 3076450 3078386 − ID = TGME49_224340; 2872 length = 1936 TGME49_chrVIII 1070714 1074839 + ID = TGME49_230880; 2873 length = 4125 TGME49_chrXI 6120810 6122479 + ID = TGME49_216480; 2874 length = 1669 TGME49_chrXI 1268350 1270276 − ID = TGME49_310330; 2875 length = 1926 TGME49_chrVIII 3749856 3752478 + ID = TGME49_272740; 2876 length = 2622 TGME49_chrX 1479988 1481931 + ID = TGME49_226620; 2877 length = 1943 TGME49_chrXI 5886992 5889236 + ID = TGME49_216780; 2878 length = 2244 TGME49_chrX 952154 954291 − ID = TGME49_227420; 2879 length = 2137 TGME49_chrVIIa 1028911 1033633 − ID = TGME49_206390; 2880 length = 4722 TGME49_chrX 4474277 4477145 − ID = TGME49_234570; 2881 length = 2868 TGME49_chrVIII 1404701 1406518 + ID = TGME49_231410; 2882 length = 1817 TGME49_chrV 374249 377042 − ID = TGME49_220430; 2883 length = 2793 TGME49_chrX 3360958 3364401 − ID = TGME49_224060; 2884 length = 3443 TGME49_chrXII 3454490 3456588 + ID = TGME49_247648; 2885 length = 2098 TGME49_chrVI 2498549 2500123 + ID = TGME49_243280; 2886 length = 1574 TGME49_chrXI 2440230 2444604 + ID = TGME49_312130; 2887 length = 4374 TGME49_chrIX 652699 656532 + ID = TGME49_267430; 2888 length = 3833 TGME49_chrVIII 5516858 5520480 + ID = TGME49_269930; 2889 length = 3622 TGME49_chrXII 5130690 5133986 + ID = TGME49_250700; 2890 length = 3296 TGME49_chrX 6943159 6945000 + ID = TGME49_215410; 2891 length = 1841 TGME49_chrIV 2086998 2089481 + ID = TGME49_210760; 2892 length = 2483 TGME49_chrIX 5323005 5326221 + ID = TGME49_305270; 2893 length = 3216 TGME49_chrVIII 6235276 6239397 + ID = TGME49_268870; 2894 length = 4121 TGME49_chrVIII 6571884 6573723 − ID = TGME49_268290; 2895 length = 1839 TGME49_chrX 7064259 7067143 + ID = TGME49_215650; 2896 length = 2884 TGME49_chrVIIb 736866 738425 − ID = TGME49_263190; 2897 length = 1559 TGME49_chrX 3318080 3319616 − ID = TGME49_224120; 2898 length = 1536 TGME49_chrIV 1113568 1114995 − ID = TGME49_318738; 2899 length = 1427 TGME49_chrX 3417971 3419580 + ID = TGME49_223970; 2900 length = 1609 TGME49_chrII 1643140 1646065 + ID = TGME49_297270; 2901 length = 2925 TGME49_chrIX 2241950 2246458 + ID = TGME49_264430; 2902 length = 4508 TGME49_chrII 892236 894195 + ID = TGME49_222130; 2903 length = 1959 TGME49_chrII 775384 778953 + ID = TGME49_222040; 2904 length = 3569 TGME49_chrVIII 6236000 6240061 − ID = TGME49_268880; 2905 length = 4061 TGME49_chrXI 1487516 1489916 + ID = TGME49_310630; 2906 length = 2400 TGME49_chrXI 4480297 4482368 + ID = TGME49_315120; 2907 length = 2071 TGME49_chrV 651209 653981 + ID = TGME49_212860; 2908 length = 2772 TGME49_chrXII 5634615 5636719 − ID = TGME49_251860; 2909 length = 2104 TGME49_chrIX 5826709 5829287 − ID = TGME49_306195; 2910 length = 2578 TGME49_chrVIIb 4025611 4030642 + ID = TGME49_257470; 2911 length = 5031 TGME49_chrIb 726992 728777 − ID = TGME49_208490; 2912 length = 1785 TGME49_chrVIIb 3639823 3643240 − ID = TGME49_258030; 2913 length = 3417 TGME49_chrX 183654 185507 + ID = TGME49_228720; 2914 length = 1853 TGME49_chrX 1104418 1106139 + ID = TGME49_227060; 2915 length = 1721 TGME49_chrVIII 265034 267090 − ID = TGME49_229450; 2916 length = 2056 TGME49_chrXII 2685283 2688777 + ID = TGME49_246160; 2917 length = 3494 TGME49_chrXII 1493469 1496095 − ID = TGME49_218500; 2918 length = 2626 TGME49_chrX 293471 295200 + ID = TGME49_228470; 2919 length = 1729 TGME49_chrIa 1148681 1150982 + ID = TGME49_294805; 2920 length = 2301 TGME49_chrXII 5149388 5150805 − ID = TGME49_250720; 2921 length = 1417 TGME49_chrIV 2465302 2467886 + ID = TGME49_301420; 2922 length = 2584 TGME49_chrVI 902188 906938 + ID = TGME49_239780; 2923 length = 4750 TGME49_chrVIIb 511337 515116 + ID = TGME49_263505; 2924 length = 3779 TGME49_chrIa 50386 52683 − ID = TGME49_292960; 2925 length = 2297 TGME49_chrIb 1410398 1412319 − ID = TGME49_209710; 2926 length = 1921 TGME49_chrII 60741 63309 − ID = TGME49_220910; 2927 length = 2568 TGME49_chrXI 2502970 2504148 + ID = TGME49_312210; 2928 length = 1178 TGME49_chrIX 979074 983263 − ID = TGME49_266760; 2929 length = 4189 TGME49_chrVIII 5800277 5801876 − ID = TGME49_269438; 2930 length = 1599 TGME49_chrXI 6434992 6437143 − ID = TGME49_216053; 2931 length = 2151 TGME49_chrXII 1281017 1283487 + ID = TGME49_218810; 2932 length = 2470 TGME49_chrX 6632419 6636375 + ID = TGME49_214970; 2933 length = 3956 TGME49_chrII 2224182 2225712 + ID = TGME49_298050; 2934 length = 1530 TGME49_chrXII 1252520 1254167 − ID = TGME49_218850; 2935 length = 1647 TGME49_chrXI 201833 203587 + ID = TGME49_306900; 2936 length = 1754 TGME49_chrII 1937751 1940101 + ID = TGME49_297720; 2937 length = 2350 TGME49_chrXI 1643494 1645015 − ID = TGME49_310880; 2938 length = 1521 TGME49_chrIa 1626000 1628841 − ID = TGME49_295662; 2939 length = 2841 TGME49_chrIb 643892 647186 − ID = TGME49_208380; 2940 length = 3294 TGME49_chrX 6495939 6497510 − ID = TGME49_214783; 2941 length = 1571 TGME49_chrX 3324291 3327072 + ID = TGME49_224090; 2942 length = 2781 TGME49_chrII 1010666 1012466 − ID = TGME49_222280; 2943 length = 1800 TGME49_chrIV 2377638 2379502 + ID = TGME49_301300; 2944 length = 1864 TGME49_chrIV 953527 955274 + ID = TGME49_319500; 2945 length = 1747 TGME49_chrX 6767415 6769751 − ID = TGME49_215110; 2946 length = 2336 TGME49_chrVIIb 2029278 2031836 − ID = TGME49_260820; 2947 length = 2558 TGME49_chrIX 254786 256497 − ID = TGME49_279340; 2948 length = 1711 TGME49_chrXII 1756941 1759557 + ID = TGME49_217340; 2949 length = 2616 TGME49_chrXI 4121268 4122993 + ID = TGME49_314480; 2950 length = 1725 TGME49_chrIX 3847198 3850189 + ID = TGME49_290700; 2951 length = 2991 TGME49_chrIX 5199766 5203644 + ID = TGME49_305050; 2952 length = 3878 TGME49_chrVIIa 969639 972289 + ID = TGME49_206440; 2953 length = 2650 TGME49_chrIb 140290 142474 + ID = TGME49_207590; 2954 length = 2184 TGME49_chrIb 1109164 1113311 − ID = TGME49_209190; 2955 length = 4147 TGME49_chrX 2374165 2376239 + ID = TGME49_225250; 2956 length = 2074 TGME49_chrVI 2345044 2347093 + ID = TGME49_242840; 2957 length = 2049 TGME49_chrIX 1613783 1618496 + ID = TGME49_265320; 2958 length = 4713 TGME49_chrXI 3994405 3998830 + ID = TGME49_314320; 2959 length = 4425 TGME49_chrV 1686358 1689982 − ID = TGME49_286760; 2960 length = 3624 TGME49_chrXI 2907482 2911745 − ID = TGME49_312690; 2961 length = 4263 TGME49_chrVI 883138 887371 + ID = TGME49_239748; 2962 length = 4233 TGME49_chrX 2183300 2187485 + ID = TGME49_225520; 2963 length = 4185 TGME49_chrXI 5574723 5577030 + ID = TGME49_316770; 2964 length = 2307 TGME49_chrII 531485 533086 + ID = TGME49_221665; 2965 length = 1601 TGME49_chrIX 3510218 3512191 + ID = TGME49_289900; 2966 length = 1973 TGME49_chrX 6214945 6217062 + ID = TGME49_214290; 2967 length = 2117 TGME49_chrVIIb 2983618 2984755 − ID = TGME49_259080; 2968 length = 1137 TGME49_chrVIIb 157650 161052 − ID = TGME49_264140; 2969 length = 3402 TGME49_chrXII 353508 355474 − ID = TGME49_299780; 2970 length = 1966 TGME49_chrX 3193336 3197198 + ID = TGME49_224235; 2971 length = 3862 TGME49_chrXII 351854 354229 + ID = TGME49_299670; 2972 length = 2375 TGME49_chrVIIb 4691742 4696076 + ID = TGME49_255730; 2973 length = 4334 TGME49_chrVIII 2314750 2316635 − ID = TGME49_232980; 2974 length = 1885 TGME49_chrIb 1053747 1054786 − ID = TGME49_209112; 2975 length = 1039 TGME49_chrVI 1271088 1275407 − ID = TGME49_240410; 2976 length = 4319 TGME49_chrIX 1913750 1916033 − ID = TGME49_264900; 2977 length = 2283 TGME49_chrX 691619 694702 + ID = TGME49_227980; 2978 length = 3083 TGME49_chrVIII 5629048 5630894 + ID = TGME49_269740; 2979 length = 1846 TGME49_chrVIIb 3410289 3414291 − ID = TGME49_258458; 2980 length = 4002 TGME49_chrVIII 6430030 6432264 − ID = TGME49_268570; 2981 length = 2234 TGME49_chrIV 1221132 1223825 − ID = TGME49_318570; 2982 length = 2693 TGME49_chrVIII 2137156 2141623 − ID = TGME49_232520; 2983 length = 4467 TGME49_chrIb 928521 933382 − ID = TGME49_208970; 2984 length = 4861 TGME49_chrVIIa 89778 91426 − ID = TGME49_280790; 2985 length = 1648 TGME49_chrIX 2800240 2802305 + ID = TGME49_288910; 2986 length = 2065 TGME49_chrV 584166 587344 − ID = TGME49_212760; 2987 length = 3178 TGME49_chrVIII 5602273 5604583 + ID = TGME49_269770; 2988 length = 2310 TGME49_chrX 4428749 4429928 + ID = TGME49_234507; 2989 length = 1179 TGME49_chrXII 1198382 1200277 − ID = TGME49_218950; 2990 length = 1895 TGME49_chrX 274179 278462 − ID = TGME49_228620; 2991 length = 4283 TGME49_chrIV 1177760 1179793 + ID = TGME49_318620; 2992 length = 2033 TGME49_chrIa 547592 550266 + ID = TGME49_293770; 2993 length = 2674 TGME49_chrXI 6518085 6519956 ID = TGME49_215940; 2994 length = 1871 TGME49_chrVI 1400236 1402037 + ID = TGME49_240710; 2995 length = 1801 TGME49_chrXII 3705841 3707649 − ID = TGME49_248150; 2996 length = 1808 TGME49_chrX 6868965 6872314 − ID = TGME49_215260; 2997 length = 3349 TGME49_chrIX 4980085 4983371 − ID = TGME49_307570; 2998 length = 3286 TGME49_chrIX 6241762 6243674 − ID = TGME49_306650; 2999 length = 1912 TGME49_chrX 7014609 7017444 + ID = TGME49_215560; 3000 length = 2835 TGME49_chrXI 3686860 3689632 − ID = TGME49_313770; 3001 length = 2772 TGME49_chrIX 2632220 2636771 − ID = TGME49_288600; 3002 length = 4551 TGME49_chrII 83969 86643 + ID = TGME49_220950; 3003 length = 2674 TGME49_chrVIIb 4483832 4488559 + ID = TGME49_256700; 3004 length = 4727 TGME49_chrVIIb 920403 922803 + ID = TGME49_262920; 3005 length = 2400 TGME49_chrIX 3726863 3728579 − ID = TGME49_290340; 3006 length = 1716 TGME49_chrIV 2265513 2268004 − ID = TGME49_301000; 3007 length = 2491 TGME49_chrVIII 4617442 4619870 − ID = TGME49_271270; 3008 length = 2428 TGME49_chrVIII 4916184 4918619 − ID = TGME49_270880; 3009 length = 2435 TGME49_chrXI 541082 545032 − ID = TGME49_309180; 3010 length = 3950 TGME49_chrVI 1421170 1423356 − ID = TGME49_240730; 3011 length = 2186 TGME49_chrX 5311235 5312787 + ID = TGME49_236190; 3012 length = 1552 TGME49_chrVIIa 1934090 1936122 − ID = TGME49_204270; 3013 length = 2032 TGME49_chrX 3689921 3692588 + ID = TGME49_223620; 3014 length = 2667 TGME49_chrIV 666975 669700 − ID = TGME49_319920; 3015 length = 2725 TGME49_chrVIII 2702317 2704841 + ID = TGME49_233540; 3016 length = 2524 TGME49_chrXII 4230314 4232511 − ID = TGME49_248860; 3017 length = 2197 TGME49_chrXI 2675685 2678516 + ID = TGME49_312430; 3018 length = 2831 TGME49_chrXII 4242327 4243685 − ID = TGME49_248880; 3019 length = 1358 TGME49_chrVIIa 3478649 3480506 − ID = TGME49_202255; 3020 length = 1857 TGME49_chrXII 157841 160945 − ID = TGME49_300220; 3021 length = 3104 TGME49_chrIX 1858908 1862051 + ID = TGME49_264990; 3022 length = 3143 TGME49_chrIV 1126774 1128732 − ID = TGME49_318720; 3023 length = 1958 TGME49_chrVIIb 342230 347024 − ID = TGME49_263750; 3024 length = 4794 TGME49_chrVIIa 3431716 3434599 + ID = TGME49_202300; 3025 length = 2883 TGME49_chrIX 3364029 3366093 − ID = TGME49_289640; 3026 length = 2064 TGME49_chrIV 1846118 1847509 + ID = TGME49_211300; 3027 length = 1391 TGME49_chrVI 1939321 1941969 + ID = TGME49_242290; 3028 length = 2648 TGME49_chrIb 1838024 1841751 + ID = TGME49_321390; 3029 length = 3727 TGME49_chrXII 3025443 3028262 − ID = TGME49_246930; 3030 length = 2819 TGME49_chrIb 982520 984651 − ID = TGME49_209005; 3031 length = 2131 TGME49_chrIX 5440014 5444552 + ID = TGME49_305510; 3032 length = 4538 TGME49_chrIb 1785634 1787380 − ID = TGME49_321460; 3033 length = 1746 TGME49_chrIX 1269529 1271869 − ID = TGME49_266150; 3034 length = 2340 TGME49_chrIV 136530 141115 + ID = TGME49_320680; 3035 length = 4585 TGME49_chrII 2129147 2131563 − ID = TGME49_297940; 3036 length = 2416 TGME49_chrX 5311706 5313875 − ID = TGME49_236160; 3037 length = 2169 TGME49_chrIX 1175142 1176935 − ID = TGME49_266390; 3038 length = 1793 TGME49_chrXII 3270428 3272692 + ID = TGME49_247340; 3039 length = 2264 TGME49_chrVIIa 4386523 4390549 − ID = TGME49_282110; 3040 length = 4026 TGME49_chrXI 5712542 5714427 + ID = TGME49_217020; 3041 length = 1885 TGME49_chrIb 508930 511554 − ID = TGME49_207990; 3042 length = 2624 TGME49_chrIV 509090 514052 + ID = TGME49_320090; 3043 length = 4962 TGME49_chrXII 2323596 2325670 − ID = TGME49_245500; 3044 length = 2074 TGME49_chrII 1838793 1840776 − ID = TGME49_297500; 3045 length = 1983 TGME49_chrIa 1848076 1849826 + ID = TGME49_295310; 3046 length = 1750 TGME49_chrVIIa 118366 123372 + ID = TGME49_280750; 3047 length = 5006 TGME49_chrIV 2323619 2324963 + ID = TGME49_301222; 3048 length = 1344 TGME49_chrVIIb 2525803 2527506 + ID = TGME49_260010; 3049 length = 1703 TGME49_chrVIII 2604789 2607085 − ID = TGME49_233340; 3050 length = 2296 TGME49_chrVIIb 629441 632828 − ID = TGME49_263327; 3051 length = 3387 TGME49_chrVI 718257 722058 − ID = TGME49_239490; 3052 length = 3801 TGME49_chrVIII 1219171 1224214 − ID = TGME49_231060; 3053 length = 5043 TGME49_chrX 7366485 7369133 − ID = TGME49_207060; 3054 length = 2648 TGME49_chrIX 326465 328648 − ID = TGME49_267840; 3055 length = 2183 TGME49_chrVIIb 3400841 3404561 + ID = TGME49_258470; 3056 length = 3720 TGME49_chrVIII 3674014 3677250 + ID = TGME49_273075; 3057 length = 3236 TGME49_chrVIIa 2121339 2125267 − ID = TGME49_203940; 3058 length = 3928 TGME49_chrXII 2197081 2199723 + ID = TGME49_217875; 3059 length = 2642 TGME49_chrXI 569487 571481 + ID = TGME49_309230; 3060 length = 1994 TGME49_chrX 660185 662395 − ID = TGME49_228040; 3061 length = 2210 TGME49_chrVIII 2294089 2295780 − ID = TGME49_232955; 3062 length = 1691 TGME49_chrXII 5476685 5478806 − ID = TGME49_251590; 3063 length = 2121 TGME49_chrIb 633161 636374 + ID = TGME49_208370; 3064 length = 3213 TGME49_chrXII 6262592 6264233 − ID = TGME49_278170; 3065 length = 1641 TGME49_chrXII 6259327 6260911 − ID = TGME49_278180; 3066 length = 1584 TGME49_chrVIIb 2848299 2850481 + ID = TGME49_259230; 3067 length = 2182 TGME49_chrIV 1768003 1771226 + ID = TGME49_211385; 3068 length = 3223 TGME49_chrVIII 1720655 1723473 − ID = TGME49_231994; 3069 length = 2818 TGME49_chrIX 4080078 4082079 + ID = TGME49_291040; 3070 length = 2001 TGME49_chrVI 1317414 1319297 − ID = TGME49_240540; 3071 length = 1883 TGME49_chrV 1652865 1654841 + ID = TGME49_286810; 3072 length = 1976 TGME49_chrVIIb 3251619 3253665 − ID = TGME49_258700; 3073 length = 2046 TGME49_chrVIIb 1370354 1372539 + ID = TGME49_262110; 3074 length = 2185 TGME49_chrVIIb 1449509 1451279 + ID = TGME49_261970; 3075 length = 1770 TGME49_chrXI 781501 783875 − ID = TGME49_309730; 3076 length = 2374 TGME49_chrVIIb 1649346 1654154 − ID = TGME49_261580; 3077 length = 4808 TGME49_chrVIII 181487 183193 − ID = TGME49_229340; 3078 length = 1706 TGME49_chrX 2911649 2913447 − ID = TGME49_224650; 3079 length = 1798 TGME49_chrIb 306500 307968 + ID = TGME49_207810; 3080 length = 1468 TGME49_chrXII 951504 953111 − ID = TGME49_219440; 3081 length = 1607 TGME49_chrX 6921384 6924980 + ID = TGME49_215360; 3082 length = 3596 TGME49_chrIa 387758 391767 − ID = TGME49_293510; 3083 length = 4009 TGME49_chrVIIb 2729364 2731606 + ID = TGME49_259650; 3084 length = 2242 TGME49_chrX 592859 595829 − ID = TGME49_228100; 3085 length = 2970 TGME49_chrX 7029939 7032199 − ID = TGME49_215580; 3086 length = 2260 TGME49_chrIb 1191601 1193002 − ID = TGME49_209290; 3087 length = 1401 TGME49_chrX 3027268 3029865 − ID = TGME49_224500; 3088 length = 2597 TGME49_chrXII 6897732 6900123 + ID = TGME49_276830; 3089 length = 2391 TGME49_chrXII 6809802 6813303 + ID = TGME49_276980; 3090 length = 3501 TGME49_chrV 1851350 1853522 − ID = TGME49_286410; 3091 length = 2172 TGME49_chrXI 4946164 4950718 + ID = TGME49_315760; 3092 length = 4554 TGME49_chrIV 1996453 2000862 + ID = TGME49_210960; 3093 length = 4409 TGME49_chrX 7087474 7089312 + ID = TGME49_215690; 3094 length = 1838 TGME49_chrXI 2289637 2291430 − ID = TGME49_311780; 3095 length = 1793 TGME49_chrVIII 2627341 2629242 − ID = TGME49_233400; 3096 length = 1901 TGME49_chrX 6836429 6838321 + ID = TGME49_215250; 3097 length = 1892 TGME49_chrX 5400481 5403238 + ID = TGME49_236530; 3098 length = 2757 TGME49_chrV 2938627 2941078 + ID = TGME49_283820; 3099 length = 2451 TGME49_chrVIIa 1810563 1815332 + ID = TGME49_204400; 3100 length = 4769 TGME49_chrXII 5747706 5751318 + ID = TGME49_278930; 3101 length = 3612 TGME49_chrXII 6168265 6171686 − ID = TGME49_278290; 3102 length = 3421 TGME49_chrV 1344460 1347471 − ID = TGME49_213800; 3103 length = 3011 TGME49_chrII 41471 44914 − ID = TGME49_220890; 3104 length = 3443 TGME49_chrIb 709441 711471 − ID = TGME49_208430; 3105 length = 2030 TGME49_chrXII 5633131 5634774 + ID = TGME49_251870; 3106 length = 1643 TGME49_chrVIIa 1364199 1366359 + ID = TGME49_205500; 3107 length = 2160 TGME49_chrVIIb 2204527 2206884 + ID = TGME49_260490; 3108 length = 2357 TGME49_chrX 4374032 4376202 − ID = TGME49_234420; 3109 length = 2170 TGME49_chrVIII 5008760 5011510 − ID = TGME49_270770; 3110 length = 2750 TGME49_chrV 1237226 1239000 + ID = TGME49_213690; 3111 length = 1774 TGME49_chrV 955818 959487 − ID = TGME49_213360; 3112 length = 3669 TGME49_chrVIII 2206818 2209210 + ID = TGME49_232655; 3113 length = 2392 TGME49_chrX 3635680 3638226 − ID = TGME49_223725; 3114 length = 2546 TGME49_chrVI 1734581 1739230 − ID = TGME49_241830; 3115 length = 4649 TGME49_chrIV 1832476 1835918 − ID = TGME49_211320; 3116 length = 3442 TGME49_chrX 1197026 1200743 − ID = TGME49_226960; 3117 length = 3717 TGME49_chrVIII 5603298 5605973 − ID = TGME49_269775; 3118 length = 2675 TGME49_chrVIIb 3587693 3590070 − ID = TGME49_258090; 3119 length = 2377 TGME49_chrX 6305337 6307575 − ID = TGME49_214470; 3120 length = 2238 TGME49_chrX 2389500 2393945 − ID = TGME49_225230; 3121 length = 4445 TGME49_chrX 968991 973953 + ID = TGME49_227380; 3122 length = 4962 TGME49_chrII 1194300 1198358 + ID = TGME49_222700; 3123 length = 4058 TGME49_chrXII 5594326 5596456 − ID = TGME49_251800; 3124 length = 2130 TGME49_chrV 2700214 2702822 − ID = TGME49_284590; 3125 length = 2608 TGME49_chrVIII 6385919 6387483 + ID = TGME49_268630; 3126 length = 1564 TGME49_chrVIIa 2542159 2544885 − ID = TGME49_203370; 3127 length = 2726 TGME49_chrIX 4954974 4957346 − ID = TGME49_210230; 3128 length = 2372 TGME49_chrIa 1011312 1015928 − ID = TGME49_294620; 3129 length = 4616 TGME49_chrVIII 3319333 3323273 − ID = TGME49_273690; 3130 length = 3940 TGME49_chrIa 1089755 1093766 − ID = TGME49_294710; 3131 length = 4011 TGME49_chrII 683949 685295 + ID = TGME49_221905; 3132 length = 1346 TGME49_chrX 5344224 5344882 − ID = TGME49_236230; 3133 length = 658 TGME49_chrVIII 6137141 6141591 − ID = TGME49_269015; 3134 length = 4450 TGME49_chrVIII 3855036 3855734 + ID = TGME49_272593; 3135 length = 698 TGME49_chrVI 2498990 2500814 − ID = TGME49_243265; 3136 length = 1824 TGME49_chrVI 1383916 1388756 − ID = TGME49_240680; 3137 length = 4840 TGME49_chrX 1826751 1828019 − ID = TGME49_226072; 3138 length = 1268 TGME49_chrXII 4263605 4265733 − ID = TGME49_248940; 3139 length = 2128 TGME49_chrX 4833704 4835258 − ID = TGME49_235390; 3140 length = 1554 TGME49_chrIX 5492734 5495529 + ID = TGME49_305600; 3141 length = 2795 TGME49_chrIV 1597207 1599157 − ID = TGME49_211700; 3142 length = 1950 TGME49_chrVIIb 2200394 2201672 − ID = TGME49_260510; 3143 length = 1278 TGME49_chrX 6491939 6496460 + ID = TGME49_214790; 3144 length = 4521 TGME49_chrXII 929521 931802 + ID = TGME49_219450; 3145 length = 2281 TGME49_chrXII 1474197 1475820 − ID = TGME49_218540; 3146 length = 1623 TGME49_chrX 2406861 2409830 − ID = TGME49_225220; 3147 length = 2969 TGME49_chrX 1658166 1660752 − ID = TGME49_226410; 3148 length = 2586 TGME49_chrIV 2117702 2122018 − ID = TGME49_210730; 3149 length = 4316 TGME49_chrVI 2322359 2326694 − ID = TGME49_242820; 3150 length = 4335 TGME49_chrX 6720390 6721912 − ID = TGME49_215050; 3151 length = 1522 TGME49_chrXII 3330336 3332740 − ID = TGME49_247410; 3152 length = 2404 TGME49_chrX 4799828 4801328 + ID = TGME49_235360; 3153 length = 1500 TGME49_chrX 1080206 1081448 − ID = TGME49_227130; 3154 length = 1242 TGME49_chrXII 1529034 1531895 − ID = TGME49_218420; 3155 length = 2861 TGME49_chrXI 4761956 4764431 + ID = TGME49_315510; 3156 length = 2475 TGME49_chrXII 4506382 4509664 + ID = TGME49_249390; 3157 length = 3282 TGME49_chrX 1539018 1541043 + ID = TGME49_226550; 3158 length = 2025 TGME49_chrX 676709 678567 + ID = TGME49_228000; 3159 length = 1858 TGME49_chrXII 6040410 6044218 + ID = TGME49_278518; 3160 length = 3808 TGME49_chrVIIa 2053467 2056236 ID = TGME49_204000; 3161 length = 2769 TGME49_chrIX 674942 676609 − ID = TGME49_267400; 3162 length = 1667 TGME49_chrV 1174251 1179266 + ID = TGME49_213620; 3163 length = 5015 TGME49_chrIb 1074486 1077281 − ID = TGME49_209140; 3164 length = 2795 TGME49_chrXI 3475816 3477674 − ID = TGME49_313560; 3165 length = 1858 TGME49_chrXI 293500 294822 + ID = TGME49_308840; 3166 length = 1322 TGME49_chrXI 2557571 2561791 − ID = TGME49_312270; 3167 length = 4220 TGME49_chrVIII 4531960 4533762 + ID = TGME49_271375; 3168 length = 1802 TGME49_chrXI 3875153 3877145 − ID = TGME49_314000; 3169 length = 1992 TGME49_chrVIIb 214816 216778 + ID = TGME49_264050; 3170 length = 1962 TGME49_chrXII 3488810 3491174 + ID = TGME49_247690; 3171 length = 2364 TGME49_chrXI 156674 158998 − ID = TGME49_306960; 3172 length = 2324 TGME49_chrVI 1295147 1297637 − ID = TGME49_240490; 3173 length = 2490 TGME49_chrXI 5342954 5345109 + ID = TGME49_316490; 3174 length = 2155 TGME49_chrVIIb 3590265 3592441 + ID = TGME49_258080; 3175 length = 2176 TGME49_chrXI 1590207 1593920 − ID = TGME49_310780; 3176 length = 3713 TGME49_chrX 5240808 5243220 − ID = TGME49_236010; 3177 length = 2412 TGME49_chrIX 2095104 2097103 − ID = TGME49_264720; 3178 length = 1999 TGME49_chrXI 2343071 2344870 − ID = TGME49_311870; 3179 length = 1799 TGME49_chrVIII 6268529 6273255 + ID = TGME49_268820; 3180 length = 4726 TGME49_chrX 5004448 5006565 + ID = TGME49_235640; 3181 length = 2117 TGME49_chrXI 1373831 1375397 + ID = TGME49_310470; 3182 length = 1566 TGME49_chrIX 5257875 5261530 + ID = TGME49_305170; 3183 length = 3655 TGME49_chrXII 1897106 1899724 + ID = TGME49_217550; 3184 length = 2618 TGME49_chrXII 6036700 6038574 + ID = TGME49_278530; 3185 length = 1874 TGME49_chrVIIa 3793013 3794469 − ID = TGME49_201785; 3186 length = 1456 TGME49_chrVIIa 4025422 4029337 + ID = TGME49_201120; 3187 length = 3915 TGME49_chrV 581559 583050 − ID = TGME49_212750; 3188 length = 1491 TGME49_chrXII 5992156 5994337 + ID = TGME49_278620; 3189 length = 2181 TGME49_chrVI 554234 557286 + ID = TGME49_239340; 3190 length = 3052 TGME49_chrXI 6472869 6475497 + ID = TGME49_216000; 3191 length = 2628 TGME49_chrIX 3637783 3640204 − ID = TGME49_290190; 3192 length = 2421 TGME49_chrVI 2669369 2670449 + ID = TGME49_243490; 3193 length = 1080 TGME49_chrXII 3820580 3822334 + ID = TGME49_248350; 3194 length = 1754 TGME49_chrV 695402 700329 − ID = TGME49_212900; 3195 length = 4927 TGME49_chrXI 3960715 3962825 + ID = TGME49_314250; 3196 length = 2110 TGME49_chrVIIb 3619190 3621196 + ID = TGME49_258050; 3197 length = 2006 TGME49_chrIX 2493133 2494671 − ID = TGME49_288390; 3198 length = 1538 TGME49_chrX 3691463 3693211 − ID = TGME49_223630; 3199 length = 1748 TGME49_chrX 2407746 2409830 − ID = TGME49_225210; 3200 length = 2084 TGME49_chrVIIa 1171935 1174196 − ID = TGME49_205760; 3201 length = 2261 TGME49_chrX 5661881 5663299 − ID = TGME49_237000; 3202 length = 1418 TGME49_chrX 6515604 6517875 + ID = TGME49_214830; 3203 length = 2271 TGME49_chrII 364035 366572 + ID = TGME49_221460; 3204 length = 2537 TGME49_chrVIII 3181451 3182748 − ID = TGME49_273915; 3205 length = 1297 TGME49_chrXI 2990969 2994121 + ID = TGME49_312950; 3206 length = 3152 TGME49_chrXI 3807555 3811116 + ID = TGME49_313930; 3207 length = 3561 TGME49_chrVIIb 3951522 3953639 + ID = TGME49_257595; 3208 length = 2117 TGME49_chrX 4325394 4329853 + ID = TGME49_234380; 3209 length = 4459 TGME49_chrVIII 6386810 6388130 − ID = TGME49_268640; 3210 length = 1320 TGME49_chrVIIa 1076863 1079600 + ID = TGME49_206290; 3211 length = 2737 TGME49_chrIX 1261687 1263721 − ID = TGME49_266270; 3212 length = 2034 TGME49_chrV 160175 161766 + ID = TGME49_220140; 3213 length = 1591 TGME49_chrVIII 5945676 5948163 + ID = TGME49_269280; 3214 length = 2487 TGME49_chrXI 3960715 3965719 + ID = TGME49_314260; 3215 length = 5004 TGME49_chrXII 2765307 2768904 + ID = TGME49_246340; 3216 length = 3597 TGME49_chrVI 2079734 2081710 + ID = TGME49_242590; 3217 length = 1976 TGME49_chrIV 2078838 2080697 + ID = TGME49_210778; 3218 length = 1859 TGME49_chrVIIa 717178 721171 + ID = TGME49_206695; 3219 length = 3993 TGME49_chrXII 440948 443883 − ID = TGME49_307840; 3220 length = 2935 TGME49_chrXI 3698435 3702023 + ID = TGME49_313810; 3221 length = 3588 TGME49_chrVIII 3942775 3945251 − ID = TGME49_272490; 3222 length = 2476 TGME49_chrVIIa 609399 611880 − ID = TGME49_304650; 3223 length = 2481 TGME49_chrVIII 759334 761144 − ID = TGME49_230410; 3224 length = 1810 TGME49_chrX 6801459 6804369 + ID = TGME49_215180; 3225 length = 2910 TGME49_chrXI 2039625 2043830 + ID = TGME49_311390; 3226 length = 4205 TGME49_chrXII 4548008 4550577 − ID = TGME49_249450; 3227 length = 2569 TGME49_chrXII 3071741 3075581 + ID = TGME49_246990; 3228 length = 3840 TGME49_chrVIII 555529 558130 − ID = TGME49_230020; 3229 length = 2601 TGME49_chrIX 2625217 2629487 − ID = TGME49_288570; 3230 length = 4270 TGME49_chrVIII 4338895 4341797 + ID = TGME49_271820; 3231 length = 2902 TGME49_chrXI 5023123 5027594 − ID = TGME49_315845; 3232 length = 4471 TGME49_chrXI 3894915 3895467 + ID = TGME49_314038; 3233 length = 552 TGME49_chrX 592274 594953 + ID = TGME49_228080; 3234 length = 2679 TGME49_chrVIIa 790922 794038 − ID = TGME49_206605; 3235 length = 3116 TGME49_chrX 12618 17436 − ID = TGME49_200700; 3236 length = 4818 TGME49_chrII 113565 116395 + ID = TGME49_221190; 3237 length = 2830 TGME49_chrXI 1603620 1606558 + ID = TGME49_310810; 3238 length = 2938 TGME49_chrXII 5728540 5730511 − ID = TGME49_278960; 3239 length = 1971 TGME49_chrVIII 2113265 2117768 − ID = TGME49_232450; 3240 length = 4503 TGME49_chrVI 2693010 2694809 − ID = TGME49_243510; 3241 length = 1799 TGME49_chrXII 2133547 2135173 − ID = TGME49_217790; 3242 length = 1626 TGME49_chrX 439688 443866 − ID = TGME49_228290; 3243 length = 4178 TGME49_chrXI 838551 840380 − ID = TGME49_309840; 3244 length = 1829 TGME49_chrVI 910173 911950 + ID = TGME49_239790; 3245 length = 1777 TGME49_chrXI 5861035 5863057 − ID = TGME49_216830; 3246 length = 2022 TGME49_chrVIII 2085152 2087343 − ID = TGME49_232420; 3247 length = 2191 TGME49_chrXI 6457120 6462057 + ID = TGME49_216020; 3248 length = 4937 TGME49_chrXI 4837616 4841215 + ID = TGME49_315600; 3249 length = 3599 TGME49_chrVIIb 696220 698492 + ID = TGME49_263220; 3250 length = 2272 TGME49_chrXI 5253011 5255174 − ID = TGME49_316350; 3251 length = 2163 TGME49_chrXI 6203760 6205467 + ID = TGME49_216370; 3252 length = 1707 TGME49_chrVIII 5584745 5587000 − ID = TGME49_269840; 3253 length = 2255 TGME49_chrVIIa 546593 549758 + ID = TGME49_304630; 3254 length = 3165 TGME49_chrIb 1563716 1566724 + ID = TGME49_209945; 3255 length = 3008 TGME49_chrVI 16939 19862 − ID = TGME49_238020; 3256 length = 2923 TGME49_chrVIII 4444950 4446452 − ID = TGME49_271625; 3257 length = 1502 TGME49_chrVIIa 4276998 4281215 − ID = TGME49_281920; 3258 length = 4217 TGME49_chrIa 512763 514787 − ID = TGME49_293690; 3259 length = 2024 TGME49_chrXII 54016 56494 − ID = TGME49_300360; 3260 length = 2478 TGME49_chrVIII 5238119 5240134 − ID = TGME49_270450; 3261 length = 2015 TGME49_chrX 3660096 3662573 + ID = TGME49_223672; 3262 length = 2477 TGME49_chrIV 1137830 1140106 + ID = TGME49_318700; 3263 length = 2276 TGME49_chrVIII 5285859 5288814 + ID = TGME49_270300; 3264 length = 2955 TGME49_chrVI 546954 551539 + ID = TGME49_239330; 3265 length = 4585 TGME49_chrVI 94162 97062 − ID = TGME49_238165; 3266 length = 2900 TGME49_chrXII 5675187 5677936 + ID = TGME49_251940; 3267 length = 2749 TGME49_chrVIII 6560093 6561570 − ID = TGME49_268300; 3268 length = 1477 TGME49_chrXII 5992982 5995016 − ID = TGME49_278630; 3269 length = 2034 TGME49_chrXI 2203975 2206339 − ID = TGME49_311680; 3270 length = 2364 TGME49_chrXII 2855036 2857439 − ID = TGME49_246555; 3271 length = 2403 TGME49_chrVIII 5713358 5716949 + ID = TGME49_269650; 3272 length = 3591 TGME49_chrVIIb 1063168 1067088 − ID = TGME49_262720; 3273 length = 3920 TGME49_chrX 4603574 4605486 − ID = TGME49_235010; 3274 length = 1912 TGME49_chrII 1076568 1079158 + ID = TGME49_222370; 3275 length = 2590 TGME49_chrVIII 367389 369573 − ID = TGME49_229650; 3276 length = 2184 TGME49_chrXII 3099886 3101996 + ID = TGME49_247010; 3277 length = 2110 TGME49_chrVIIb 1127048 1129656 + ID = TGME49_262610; 3278 length = 2608 TGME49_chrVIII 3232358 3234398 + ID = TGME49_273830; 3279 length = 2040 TGME49_chrVIII 3923611 3925862 + ID = TGME49_272520; 3280 length = 2251 TGME49_chrIV 278199 282008 − ID = TGME49_320540; 3281 length = 3809 TGME49_chrX 493321 495081 − ID = TGME49_228210; 3282 length = 1760 TGME49_chrVIII 1768528 1773014 + ID = TGME49_232030; 3283 length = 4486 TGME49_chrVIII 5272156 5276079 − ID = TGME49_270330; 3284 length = 3923 TGME49_chrVIII 6183118 6185406 − ID = TGME49_268960; 3285 length = 2288 TGME49_chrIV 758992 760757 − ID = TGME49_319730; 3286 length = 1765 TGME49_chrIV 948350 951893 − ID = TGME49_319520; 3287 length = 3543 TGME49_chrIX 2438866 2442135 + ID = TGME49_288300; 3288 length = 3269 TGME49_chrVIIb 4640463 4643361 − ID = TGME49_255895; 3289 length = 2898 TGME49_chrX 5206510 5208863 + ID = TGME49_235970; 3290 length = 2353 TGME49_chrVIIb 4570661 4571741 − ID = TGME49_256010; 3291 length = 1080 TGME49_chrX 1627981 1632602 − ID = TGME49_226450; 3292 length = 4621 TGME49_chrXI 615166 617797 + ID = TGME49_309300; 3293 length = 2631 TGME49_chrVIII 3318828 3322791 + ID = TGME49_273670; 3294 length = 3963 TGME49_chrVIIb 856438 857983 − ID = TGME49_263050; 3295 length = 1545 TGME49_chrIX 4005052 4007328 − ID = TGME49_290970; 3296 length = 2276 TGME49_chrXI 2645045 2647433 + ID = TGME49_312380; 3297 length = 2388 TGME49_chrIb 927952 932691 + ID = TGME49_208980; 3298 length = 4739 TGME49_chrX 1515798 1517465 + ID = TGME49_226590; 3299 length = 1667 TGME49_chrX 1285743 1290308 − ID = TGME49_226860; 3300 length = 4565 TGME49_chrVIII 6167383 6169354 − ID = TGME49_268985; 3301 length = 1971 TGME49_chrX 3025485 3029064 + ID = TGME49_224490; 3302 length = 3579 TGME49_chrIV 2047627 2048983 − ID = TGME49_210800; 3303 length = 1356 TGME49_chrIX 998733 1003398 + ID = TGME49_266710; 3304 length = 4665 TGME49_chrX 4396194 4397204 + ID = TGME49_234450; 3305 length = 1010 TGME49_chrII 1112777 1115543 − ID = TGME49_222390; 3306 length = 2766 TGME49_chrIV 812222 814651 + ID = TGME49_319640; 3307 length = 2429 TGME49_chrV 1460170 1461527 + ID = TGME49_213960; 3308 length = 1357 TGME49_chrIa 182514 184547 − ID = TGME49_293230; 3309 length = 2033 TGME49_chrVIIb 2271547 2274550 + ID = TGME49_260430; 3310 length = 3003 TGME49_chrII 924486 928859 + ID = TGME49_222170; 3311 length = 4373 TGME49_chrX 1874663 1877819 ID = TGME49_226000; 3312 length = 3156 TGME49_chrIX 3289012 3292661 + ID = TGME49_289540; 3313 length = 3649 TGME49_chrXI 4923699 4926214 + ID = TGME49_315720; 3314 length = 2515 TGME49_chrXII 2633358 2636013 − ID = TGME49_246050; 3315 length = 2655 TGME49_chrVIIb 3442643 3444853 − ID = TGME49_258390; 3316 length = 2210 TGME49_chrIb 1471114 1474353 + ID = TGME49_209830; 3317 length = 3239 TGME49_chrXII 6529058 6534063 − ID = TGME49_277770; 3318 length = 5005 TGME49_chrV 423922 426714 + ID = TGME49_220510; 3319 length = 2792 TGME49_chrVIIb 1746391 1751219 − ID = TGME49_261450; 3320 length = 4828 TGME49_chrIV 1632693 1634603 − ID = TGME49_211670; 3321 length = 1910 TGME49_chrVIII 3963511 3965457 + ID = TGME49_272440; 3322 length = 1946 TGME49_chrIX 5666236 5668173 + ID = TGME49_305920; 3323 length = 1937 TGME49_chrXII 5902655 5905896 − ID = TGME49_278753; 3324 length = 3241 TGME49_chrXI 1574116 1575491 + ID = TGME49_310760; 3325 length = 1375 TGME49_chrVI 1692909 1695468 + ID = TGME49_241300; 3326 length = 2559 TGME49_chrIb 601374 605206 − ID = TGME49_208200; 3327 length = 3832 TGME49_chrXI 5520848 5523439 + ID = TGME49_316730; 3328 length = 2591 TGME49_chrXII 3127172 3130041 − ID = TGME49_247040; 3329 length = 2869 TGME49_chrIb 1399838 1402434 + ID = TGME49_209690; 3330 length = 2596 TGME49_chrX 5779951 5782510 − ID = TGME49_237200; 3331 length = 2559 TGME49_chrXII 5724237 5726426 − ID = TGME49_278965; 3332 length = 2189 TGME49_chrXI 3466374 3470440 + ID = TGME49_313550; 3333 length = 4066 TGME49_chrVIIb 4749722 4752553 + ID = TGME49_255650; 3334 length = 2831 TGME49_chrIX 5611490 5613721 + ID = TGME49_305840; 3335 length = 2231 TGME49_chrIX 4291304 4293908 − ID = TGME49_291600; 3336 length = 2604 TGME49_chrXI 3453849 3456185 + ID = TGME49_313520; 3337 length = 2336 TGME49_chrXII 4749942 4752741 + ID = TGME49_249710; 3338 length = 2799 TGME49_chrIa 1782761 1785919 + ID = TGME49_295390; 3339 length = 3158 TGME49_chrXI 732325 734891 + ID = TGME49_309580; 3340 length = 2566 TGME49_chrX 6496294 6497510 − ID = TGME49_214787; 3341 length = 1216 TGME49_chrX 3655540 3656902 − ID = TGME49_223690; 3342 length = 1362 TGME49_chrVIIb 583138 585745 − ID = TGME49_263400; 3343 length = 2607 TGME49_chrXI 175012 177263 − ID = TGME49_306940; 3344 length = 2251 TGME49_chrX 6253503 6255193 − ID = TGME49_214330; 3345 length = 1690 TGME49_chrVIII 2174546 2176594 − ID = TGME49_232580; 3346 length = 2048 TGME49_chrXI 5840587 5844665 + ID = TGME49_216860; 3347 length = 4078 TGME49_chrIb 1543519 1546904 + ID = TGME49_209910; 3348 length = 3385 TGME49_chrX 3769236 3773701 + ID = TGME49_223500; 3349 length = 4465 TGME49_chrVI 1585973 1590736 − ID = TGME49_240960; 3350 length = 4763 TGME49_chrV 609849 613843 + ID = TGME49_212810; 3351 length = 3994 TGME49_chrII 1315546 1319755 + ID = TGME49_222940; 3352 length = 4209 TGME49_chrXI 2932469 2934408 + ID = TGME49_312830; 3353 length = 1939 TGME49_chrXII 5198502 5201968 − ID = TGME49_250770; 3354 length = 3466 TGME49_chrVIII 3444778 3446250 + ID = TGME49_273490; 3355 length = 1472 TGME49_chrV 1399034 1402700 − ID = TGME49_213870; 3356 length = 3666 TGME49_chrXII 2256968 2259255 − ID = TGME49_245432; 3357 length = 2287 TGME49_chrIa 1423949 1426873 − ID = TGME49_296015; 3358 length = 2924 TGME49_chrVIIb 4379347 4381247 − ID = TGME49_256900; 3359 length = 1900 TGME49_chrIX 3193824 3196200 + ID = TGME49_289330; 3360 length = 2376 TGME49_chrXII 2463875 2465663 + ID = TGME49_245680; 3361 length = 1788 TGME49_chrXI 308195 311017 − ID = TGME49_308860; 3362 length = 2822 TGME49_chrXI 6078723 6081550 − ID = TGME49_216580; 3363 length = 2827 TGME49_chrVIII 609952 611492 − ID = TGME49_230110; 3364 length = 1540 TGME49_chrXI 378842 382347 + ID = TGME49_308950; 3365 length = 3505 TGME49_chrXII 5499356 5500559 + ID = TGME49_251630; 3366 length = 1203 TGME49_chrVI 3641420 3643484 + ID = TGME49_292610; 3367 length = 2064 TGME49_chrII 1468746 1470751 − ID = TGME49_223130; 3368 length = 2005 TGME49_chrV 1397770 1400442 + ID = TGME49_213880; 3369 length = 2672 TGME49_chrXI 1041192 1043750 − ID = TGME49_310070; 3370 length = 2558 TGME49_chrIa 837889 840906 + ID = TGME49_294360; 3371 length = 3017 TGME49_chrV 2173738 2175720 − ID = TGME49_285850; 3372 length = 1982 TGME49_chrX 6414014 6416110 − ID = TGME49_214600; 3373 length = 2096 TGME49_chrVIII 6252860 6255582 − ID = TGME49_268850; 3374 length = 2722 TGME49_chrX 1713807 1716377 − ID = TGME49_226330; 3375 length = 2570 TGME49_chrX 6206363 6211100 − ID = TGME49_214270; 3376 length = 4737 TGME49_chrXII 5579562 5582287 − ID = TGME49_251770; 3377 length = 2725 TGME49_chrIV 2065253 2067243 − ID = TGME49_210783; 3378 length = 1990 TGME49_chrVIIb 4008596 4011217 + ID = TGME49_257500; 3379 length = 2621 TGME49_chrII 1545348 1549822 + ID = TGME49_297120; 3380 length = 4474 TGME49_chrXII 3676372 3680205 − ID = TGME49_248120; 3381 length = 3833 TGME49_chrVIIa 1331384 1334559 + ID = TGME49_205558; 3382 length = 3175 TGME49_chrIX 2596471 2598483 + ID = TGME49_288530; 3383 length = 2012 TGME49_chrXI 2103770 2107867 − ID = TGME49_311470; 3384 length = 4097 TGME49_chrXII 1911601 1912822 + ID = TGME49_217570; 3385 length = 1221 TGME49_chrVIII 3216368 3219488 + ID = TGME49_273860; 3386 length = 3120 TGME49_chrVIII 4616470 4619161 + ID = TGME49_271260; 3387 length = 2691 TGME49_chrIX 6203119 6204949 − ID = TGME49_306590; 3388 length = 1830 TGME49_chrX 865963 867849 − ID = TGME49_227640; 3389 length = 1886 TGME49_chrIX 3016565 3020010 + ID = TGME49_289130; 3390 length = 3445 TGME49_chrIb 498140 499444 − ID = TGME49_207980; 3391 length = 1304 TGME49_chrX 5674742 5676571 − ID = TGME49_237015; 3392 length = 1829 TGME49_chrX 1645346 1649764 − ID = TGME49_226430; 3393 length = 4418 TGME49_chrVI 3181640 3183599 − ID = TGME49_244300; 3394 length = 1959 TGME49_chrIV 132847 135011 − ID = TGME49_320700; 3395 length = 2164 TGME49_chrIX 4534068 4536660 + ID = TGME49_292080; 3396 length = 2592 TGME49_chrIX 2631176 2636201 + ID = TGME49_288610; 3397 length = 5025 TGME49_chrVIII 3309949 3314650 − ID = TGME49_273720; 3398 length = 4701 TGME49_chrXI 6373312 6376490 − ID = TGME49_216160; 3399 length = 3178 TGME49_chrVI 2847279 2852109 + ID = TGME49_243780; 3400 length = 4830 TGME49_chrX 6937876 6940165 − ID = TGME49_215380; 3401 length = 2289 TGME49_chrIX 2722000 2725631 − ID = TGME49_288740; 3402 length = 3631 TGME49_chrXI 5792072 5794118 + ID = TGME49_216910; 3403 length = 2046 TGME49_chrVIII 1385211 1389924 + ID = TGME49_231380; 3404 length = 4713 TGME49_chrXI 3986515 3988412 + ID = TGME49_314295; 3405 length = 1897 TGME49_chrXII 2003898 2008672 − ID = TGME49_217680; 3406 length = 4774 TGME49_chrIX 530467 532341 − ID = TGME49_267600; 3407 length = 1874 TGME49_chrXI 4606041 4607359 + ID = TGME49_315260; 3408 length = 1318 TGME49_chrVIII 3576863 3580229 + ID = TGME49_273350; 3409 length = 3366 TGME49_chrII 233786 235666 − ID = TGME49_221310; 3410 length = 1880 TGME49_chrXII 4287010 4288915 + ID = TGME49_248990; 3411 length = 1905 TGME49_chrII 695953 698239 − ID = TGME49_221818; 3412 length = 2286 TGME49_chrX 6983149 6985034 + ID = TGME49_215500; 3413 length = 1885 TGME49_chrV 799775 804114 − ID = TGME49_213020; 3414 length = 4339 TGME49_chrVIIb 5061398 5064594 + ID = TGME49_255160; 3415 length = 3196 TGME49_chrVI 3417882 3420561 + ID = TGME49_244645; 3416 length = 2679 TGME49_chrXII 3073064 3076076 − ID = TGME49_246982; 3417 length = 3012 TGME49_chrVIIa 1500269 1505002 + ID = TGME49_205265; 3418 length = 4733 TGME49_chrVIII 2112448 2114445 + ID = TGME49_232475; 3419 length = 1997 TGME49_chrXII 1187769 1192566 − ID = TGME49_218960; 3420 length = 4797 TGME49_chrVI 1800045 1804730 − ID = TGME49_241880; 3421 length = 4685 TGME49_chrIX 5505937 5508990 − ID = TGME49_305610; 3422 length = 3053 TGME49_chrVI 253436 258317 − ID = TGME49_238500; 3423 length = 4881 TGME49_chrVIIb 3933802 3935262 − ID = TGME49_257650; 3424 length = 1460 TGME49_chrVIII 6330739 6334570 − ID = TGME49_268760; 3425 length = 3831 TGME49_chrVIII 793083 797090 − ID = TGME49_230440; 3426 length = 4007 TGME49_chrVIIa 186501 187589 + ID = TGME49_280680; 3427 length = 1088 TGME49_chrXII 6705701 6707565 − ID = TGME49_277220; 3428 length = 1864 TGME49_chrII 2003854 2005661 − ID = TGME49_297790; 3429 length = 1807 TGME49_chrVI 2742265 2744014 − ID = TGME49_243590; 3430 length = 1749 TGME49_chrX 7067044 7071859 − ID = TGME49_215640; 3431 length = 4815 TGME49_chrVIIa 1741358 1742899 + ID = TGME49_204505; 3432 length = 1541 TGME49_chrXI 1843155 1846445 + ID = TGME49_311180; 3433 length = 3290 TGME49_chrVI 948026 952595 − ID = TGME49_239820; 3434 length = 4569 TGME49_chrXII 1834934 1837076 − ID = TGME49_217430; 3435 length = 2142 TGME49_chrXI 3142479 3147503 + ID = TGME49_313160; 3436 length = 5024 TGME49_chrX 7130359 7132487 + ID = TGME49_215730; 3437 length = 2128 TGME49_chrVIII 2286666 2287451 − ID = TGME49_232840; 3438 length = 785 TGME49_chrXI 1636892 1638984 − ID = TGME49_310860; 3439 length = 2092 TGME49_chrVIIa 4276229 4277993 + ID = TGME49_281930; 3440 length = 1764 TGME49_chrVIII 6329519 6334023 + ID = TGME49_268750; 3441 length = 4504 TGME49_chrVI 528450 531729 − ID = TGME49_239290; 3442 length = 3279 TGME49_chrVIIa 1355067 1359343 − ID = TGME49_205530; 3443 length = 4276 TGME49_chrXI 5877907 5880229 − ID = TGME49_216800; 3444 length = 2322 TGME49_chrVIIb 2679663 2683799 − ID = TGME49_259835; 3445 length = 4136 TGME49_chrIX 5598442 5601226 − ID = TGME49_305800; 3446 length = 2784 TGME49_chrIa 676197 678509 − ID = TGME49_294100; 3447 length = 2312 TGME49_chrXII 4807452 4810501 − ID = TGME49_249800; 3448 length = 3049 TGME49_chrXI 2952334 2953239 − ID = TGME49_312850; 3449 length = 905 TGME49_chrVI 85967 88465 + ID = TGME49_238150; 3450 length = 2498 TGME49_chrVI 1774870 1776217 + ID = TGME49_241870; 3451 length = 1347 TGME49_chrX 2443820 2445343 + ID = TGME49_225160; 3452 length = 1523 TGME49_chrV 2256865 2258465 + ID = TGME49_285740; 3453 length = 1600 TGME49_chrVIIa 3055087 3057294 − ID = TGME49_202760; 3454 length = 2207 TGME49_chrXI 5215999 5218760 + ID = TGME49_316270; 3455 length = 2761 TGME49_chrIV 1641289 1644518 − ID = TGME49_211650; 3456 length = 3229 TGME49_chrX 5720126 5723099 + ID = TGME49_237110; 3457 length = 2973 TGME49_chrXII 2748458 2750074 + ID = TGME49_246210; 3458 length = 1616 TGME49_chrVIII 5322899 5326644 + ID = TGME49_270220; 3459 length = 3745 TGME49_chrXII 889364 891927 − ID = TGME49_219520; 3460 length = 2563 TGME49_chrVI 1379941 1381383 + ID = TGME49_240670; 3461 length = 1442 TGME49_chrXI 1373831 1378479 + ID = TGME49_310480; 3462 length = 4648 TGME49_chrXII 1208189 1212694 − ID = TGME49_218930; 3463 length = 4505 TGME49_chrXII 3616444 3617866 − ID = TGME49_247850; 3464 length = 1422 TGME49_chrV 1485948 1487275 + ID = TGME49_287270; 3465 length = 1327 TGME49_chrV 1321800 1325747 − ID = TGME49_213780; 3466 length = 3947 TGME49_chrIV 1216840 1218366 − ID = TGME49_318580; 3467 length = 1526 TGME49_chrVIIa 3969642 3972217 − ID = TGME49_201220; 3468 length = 2575 TGME49_chrX 4930960 4934578 − ID = TGME49_235515; 3469 length = 3618 TGME49_chrX 1848514 1851776 + ID = TGME49_226040; 3470 length = 3262 TGME49_chrIa 1201664 1204376 − ID = TGME49_294830; 3471 length = 2712 TGME49_chrVIII 4210000 4212465 − ID = TGME49_272030; 3472 length = 2465 TGME49_chrXII 511743 514831 − ID = TGME49_308020; 3473 length = 3088 TGME49_chrVIIb 2608548 2610923 + ID = TGME49_259920; 3474 length = 2375 TGME49_chrX 5290611 5294071 − ID = TGME49_236120; 3475 length = 3460 TGME49_chrVIIa 3849344 3854159 + ID = TGME49_201680; 3476 length = 4815 TGME49_chrVIII 6557517 6561570 − ID = TGME49_268310; 3477 length = 4053 TGME49_chrX 5806926 5808940 − ID = TGME49_237240; 3478 length = 2014 TGME49_chrX 922178 924766 + ID = TGME49_227450; 3479 length = 2588 TGME49_chrIX 2659018 2661986 − ID = TGME49_288650; 3480 length = 2968 TGME49_chrVI 2759019 2762419 − ID = TGME49_243620; 3481 length = 3400 TGME49_chrX 6474784 6479194 + ID = TGME49_214760; 3482 length = 4410 TGME49_chrVIIb 1670163 1672456 − ID = TGME49_261530; 3483 length = 2293 TGME49_chrXI 5801565 5802917 − ID = TGME49_216900; 3484 length = 1352 TGME49_chrX 6979927 6981500 − ID = TGME49_215480; 3485 length = 1573 TGME49_chrXII 4078485 4082874 + ID = TGME49_248677; 3486 length = 4389 TGME49_chrX 153327 1537059 − ID = TGME49_226570; 3487 length = 3782 TGME49_chrIX 1670658 1673385 + ID = TGME49_265240; 3488 length = 2727 TGME49_chrX 5351130 5352320 + ID = TGME49_236250; 3489 length = 1190 TGME49_chrXII 302852 304279 − ID = TGME49_299980; 3490 length = 1427 TGME49_chrIb 1403953 1405251 + ID = TGME49_209700; 3491 length = 1298 TGME49_chrX 3003705 3007325 + ID = TGME49_224520; 3492 length = 3620 TGME49_chrIV 194285 196070 + ID = TGME49_320620; 3493 length = 1785 TGME49_chrVIII 5189323 5191091 − ID = TGME49_270570; 3494 length = 1768 TGME49_chrX 971149 975816 − ID = TGME49_227390; 3495 length = 4667 TGME49_chrV 1145386 1146565 + ID = TGME49_213560; 3496 length = 1179 TGME49_chrXII 5661190 5663297 − ID = TGME49_251910; 3497 length = 2107 TGME49_chrIb 1685989 1690920 − ID = TGME49_321630; 3498 length = 4931 TGME49_chrIa 662350 666276 + ID = TGME49_294060; 3499 length = 3926 TGME49_chrXI 3347499 3350293 + ID = TGME49_313410; 3500 length = 2794 TGME49_chrXI 611336 614210 + ID = TGME49_309290; 3501 length = 2874 TGME49_chrIX 4385909 4387593 − ID = TGME49_291860; 3502 length = 1684 TGME49_chrXII 2671176 2675189 − ID = TGME49_246110; 3503 length = 4013 TGME49_chrXII 565309 566062 − ID = TGME49_308075; 3504 length = 753 TGME49_chrXII 4727155 4729832 − ID = TGME49_249670; 3505 length = 2677 TGME49_chrVI 447757 449748 − ID = TGME49_239070; 3506 length = 1991 TGME49_chrII 287426 290540 − ID = TGME49_221360; 3507 length = 3114 TGME49_chrVIIb 1873350 1876420 + ID = TGME49_261070; 3508 length = 3070 TGME49_chrVIII 4011550 4016029 − ID = TGME49_272390; 3509 length = 4479 TGME49_chrVIII 2610522 2615562 − ID = TGME49_233360; 3510 length = 5040 TGME49_chrVIII 5437065 5439034 − ID = TGME49_270070; 3511 length = 1969 TGME49_chrVI 75690 77850 − ID = TGME49_238130; 3512 length = 2160 TGME49_chrVIIa 1530903 1532616 − ID = TGME49_205230; 3513 length = 1713 TGME49_chrVIIb 2754602 2756634 − ID = TGME49_259610; 3514 length = 2032 TGME49_chrXI 1158079 1160818 − ID = TGME49_310210; 3515 length = 2739 TGME49_chrVIII 530520 533240 − ID = TGME49_230000; 3516 length = 2720 TGME49_chrIX 5528569 5530025 + ID = TGME49_305635; 3517 length = 1456 TGME49_chrXII 1633375 1637998 + ID = TGME49_218260; 3518 length = 4623 TGME49_chrVIII 3530338 3532583 − ID = TGME49_273400; 3519 length = 2245 TGME49_chrXI 2200480 2202879 − ID = TGME49_311670; 3520 length = 2399 TGME49_chrIX 4305726 4310108 − ID = TGME49_291630; 3521 length = 4382 TGME49_chrIa 1266145 1267436 − ID = TGME49_294902; 3522 length = 1291 TGME49_chrIb 209955 214235 + ID = TGME49_207690; 3523 length = 4280 TGME49_chrXII 2858847 2863310 + ID = TGME49_246580; 3524 length = 4463 TGME49_chrXII 823067 826469 + ID = TGME49_219610; 3525 length = 3402 TGME49_chrVIIa 3833493 3834672 + ID = TGME49_201710; 3526 length = 1179 TGME49_chrVIIb 3296060 3297939 + ID = TGME49_258625; 3527 length = 1879 TGME49_chrVI 867209 869418 − ID = TGME49_239710; 3528 length = 2209 TGME49_chrVIIa 1275423 1276455 − ID = TGME49_205615; 3529 length = 1032 TGME49_chrXII 4708702 4710344 − ID = TGME49_249630; 3530 length = 1642 TGME49_chrX 4171748 4175262 − ID = TGME49_234165; 3531 length = 3514 TGME49_chrXII 120499 122563 + ID = TGME49_300260; 3532 length = 2064 TGME49_chrVI 498397 501660 − ID = TGME49_239260; 3533 length = 3263 TGME49_chrVIII 493816 497365 − ID = TGME49_229960; 3534 length = 3549 TGME49_chrVIIa 3616280 3620711 − ID = TGME49_202090; 3535 length = 4431 TGME49_chrX 6973684 6974864 − ID = TGME49_215460; 3536 length = 1180 TGME49_chrX 6725890 6729429 − ID = TGME49_215060; 3537 length = 3539 TGME49_chrXI 2762805 2765415 − ID = TGME49_312520; 3538 length = 2610 TGME49_chrVIIa 989384 994150 + ID = TGME49_206415; 3539 length = 4766 TGME49_chrIb 1033057 1035956 − ID = TGME49_209080; 3540 length = 2899 TGME49_chrVIIb 363934 367739 + ID = TGME49_263720; 3541 length = 3805 TGME49_chrIX 3679329 3681333 + ID = TGME49_290290; 3542 length = 2004 TGME49_chrXI 1327241 1328715 − ID = TGME49_310410; 3543 length = 1474 TGME49_chrIb 162965 165017 + ID = TGME49_207630; 3544 length = 2052 TGME49_chrVIII 3411630 3413948 − ID = TGME49_273550; 3545 length = 2318 TGME49_chrIX 4237613 4239542 − ID = TGME49_291310; 3546 length = 1929 TGME49_chrV 2711277 2713061 + ID = TGME49_284560; 3547 length = 1784 TGME49_chrVI 66661 71093 − ID = TGME49_238100; 3548 length = 4432 TGME49_chrIb 1108181 1112225 + ID = TGME49_209200; 3549 length = 4044 TGME49_chrX 1125018 1129103 + ID = TGME49_227030; 3550 length = 4085 TGME49_chrXII 1476720 1480771 + ID = TGME49_218510; 3551 length = 4051 TGME49_chrVIII 3028294 3030583 − ID = TGME49_274110; 3552 length = 2289 TGME49_chrIX 727730 732199 − ID = TGME49_267312; 3553 length = 4469 TGME49_chrVI 1723775 1727714 + ID = TGME49_241820; 3554 length = 3939 TGME49_chrVIII 560930 562293 + ID = TGME49_230040; 3555 length = 1363 TGME49_chrII 1419626 1421332 + ID = TGME49_223070; 3556 length = 1706 TGME49_chrXI 2816725 2818748 + ID = TGME49_312600; 3557 length = 2023 TGME49_chrX 7085873 7087326 − ID = TGME49_215680; 3558 length = 1453 TGME49_chrIV 1162958 1165755 − ID = TGME49_318675; 3559 length = 2797 TGME49_chrIV 1932608 1935398 − ID = TGME49_211150; 3560 length = 2790 TGME49_chrXII 3024176 3027111 + ID = TGME49_246940; 3561 length = 2935 TGME49_chrVIIb 1718394 1720099 + ID = TGME49_261475; 3562 length = 1705 TGME49_chrVIII 5188589 5190591 + ID = TGME49_270560; 3563 length = 2002 TGME49_chrX 6922474 6926889 − ID = TGME49_215350; 3564 length = 4415 TGME49_chrIX 2114633 2116655 + ID = TGME49_264670; 3565 length = 2022 TGME49_chrIX 5302620 5305770 + ID = TGME49_305240; 3566 length = 3150 TGME49_chrXI 3722265 3724229 + ID = TGME49_313840; 3567 length = 1964 TGME49_chrX 3679396 3681487 + ID = TGME49_223650; 3568 length = 2091 TGME49_chrXI 1612255 1614074 + ID = TGME49_310820; 3569 length = 1819 TGME49_chrXI 4303663 4305739 − ID = TGME49_314790; 3570 length = 2076 TGME49_chrVIIa 3037960 3042664 − ID = TGME49_202780; 3571 length = 4704 TGME49_chrVIII 5353669 5354773 + ID = TGME49_270180; 3572 length = 1104 TGME49_chrXI 5186674 5188879 + ID = TGME49_316220; 3573 length = 2205 TGME49_chrXII 6491430 6491855 − ID = TGME49_277830; 3574 length = 425 TGME49_chrIV 1178360 1180121 − ID = TGME49_318640; 3575 length = 1761 TGME49_chrIb 1391208 1393087 + ID = TGME49_209670; 3576 length = 1879 TGME49_chrIb 801471 804370 + ID = TGME49_208590; 3577 length = 2899 TGME49_chrVIII 415461 417463 − ID = TGME49_229740; 3578 length = 2002 TGME49_chrII 1274986 1276921 + ID = TGME49_222880; 3579 length = 1935 TGME49_chrX 2466640 2469050 + ID = TGME49_225125; 3580 length = 2410 TGME49_chrVIIb 3277596 3280720 − ID = TGME49_258660; 3581 length = 3124 TGME49_chrVIIb 1395785 1399179 − ID = TGME49_262070; 3582 length = 3394 TGME49_chrXII 6597047 6599362 + ID = TGME49_277560; 3583 length = 2315 TGME49_chrX 7215853 7217846 − ID = TGME49_275380; 3584 length = 1993 TGME49_chrX 6766166 6769751 − ID = TGME49_215100; 3585 length = 3585 TGME49_chrX 5386834 5389094 − ID = TGME49_236400; 3586 length = 2260 TGME49_chrII 1531544 1535065 − ID = TGME49_297100; 3587 length = 3521 TGME49_chrXI 2073091 2077650 − ID = TGME49_311440; 3588 length = 4559 TGME49_chrVIIa 3216124 3218042 − ID = TGME49_202572; 3589 length = 1918 TGME49_chrIa 1388041 1391447 + ID = TGME49_295090; 3590 length = 3406 TGME49_chrX 896541 897868 − ID = TGME49_227600; 3591 length = 1327 TGME49_chrXII 6222021 6223691 − ID = TGME49_278230; 3592 length = 1670 TGME49_chrIX 5825997 5828317 + ID = TGME49_306210; 3593 length = 2320 TGME49_chrX 3282886 3284073 + ID = TGME49_224170; 3594 length = 1187 TGME49_chrVIII 377418 380433 − ID = TGME49_229680; 3595 length = 3015 TGME49_chrV 3104191 3107086 + ID = TGME49_283510; 3596 length = 2895 TGME49_chrV 2202009 2203415 − ID = TGME49_285820; 3597 length = 1406 TGME49_chrIV 1970430 1971908 − ID = TGME49_211015; 3598 length = 1478 TGME49_chrVI 1052919 1057698 + ID = TGME49_240090; 3599 length = 4779 TGME49_chrVI 1330533 1332686 − ID = TGME49_240580; 3600 length = 2153 TGME49_chrX 5296360 5298183 + ID = TGME49_236140; 3601 length = 1823 TGME49_chrVIIa 1575851 1578088 + ID = TGME49_205150; 3602 length = 2237 TGME49_chrVIIb 3668995 3670754 + ID = TGME49_257990; 3603 length = 1759 TGME49_chrIb 27811 29823 + ID = TGME49_207400; 3604 length = 2012 TGME49_chrVIII 3674014 3678518 + ID = TGME49_273070; 3605 length = 4504 TGME49_chrIV 2020728 2022776 + ID = TGME49_210830; 3606 length = 2048 TGME49_chrIa 501242 504308 + ID = TGME49_293680; 3607 length = 3066 TGME49_chrVIII 4188294 4190240 + ID = TGME49_272040; 3608 length = 1946 TGME49_chrVIIb 1593274 1595045 + ID = TGME49_261670; 3609 length = 1771 TGME49_chrVI 2345044 2347765 + ID = TGME49_242845; 3610 length = 2721 TGME49_chrVIIb 892798 896825 + ID = TGME49_262960; 3611 length = 4027 TGME49_chrVIIb 4576535 4578100 − ID = TGME49_255990; 3612 length = 1565 TGME49_chrVIIb 3564269 3567431 − ID = TGME49_258120; 3613 length = 3162 TGME49_chrV 841156 844040 − ID = TGME49_213067; 3614 length = 2884 TGME49_chrVIIb 400077 401984 − ID = TGME49_263680; 3615 length = 1907 TGME49_chrVIII 5651257 5654273 − ID = TGME49_269720; 3616 length = 3016 TGME49_chrXI 5824519 5825439 − ID = TGME49_216875; 3617 length = 920 TGME49_chrIa 289525 291377 − ID = TGME49_293370; 3618 length = 1852 TGME49_chrVIIb 340984 345618 + ID = TGME49_263740; 3619 length = 4634 TGME49_chrVI 3334624 3336932 − ID = TGME49_244515; 3620 length = 2308 TGME49_chrVIII 6462178 6464044 + ID = TGME49_268390; 3621 length = 1866 TGME49_chrII 1825535 1830439 − ID = TGME49_297495; 3622 length = 4904 TGME49_chrVI 151812 155358 + ID = TGME49_238250; 3623 length = 3546 TGME49_chrX 4153234 4155867 + ID = TGME49_211870; 3624 length = 2633 TGME49_chrVIIa 3118368 3121954 − ID = TGME49_202660; 3625 length = 3586 TGME49_chrXII 3689537 3692256 − ID = TGME49_248140; 3626 length = 2719 TGME49_chrXI 3279967 3283134 − ID = TGME49_313330; 3627 length = 3167 TGME49_chrVIII 3960669 3963072 − ID = TGME49_272460; 3628 length = 2403 TGME49_chrX 5463469 5465206 − ID = TGME49_236635; 3629 length = 1737 TGME49_chrV 1402650 1404500 + ID = TGME49_213890; 3630 length = 1850 TGME49_chrX 4153234 4155275 + ID = TGME49_211880; 3631 length = 2041 TGME49_chrX 1266993 1269615 + ID = TGME49_226880; 3632 length = 2622 TGME49_chrIX 1528778 1530786 + ID = TGME49_265480; 3633 length = 2008 TGME49_chrIX 1745845 1747343 − ID = TGME49_265150; 3634 length = 1498 TGME49_chrVI 884386 888183 − ID = TGME49_239740; 3635 length = 3797 TGME49_chrXI 5317194 5320938 + ID = TGME49_316460; 3636 length = 3744 TGME49_chrVIIb 776365 780112 + ID = TGME49_263130; 3637 length = 3747 TGME49_chrXI 6442825 6444555 − ID = TGME49_216050; 3638 length = 1730 TGME49_chrX 2318525 2320515 + ID = TGME49_225310; 3639 length = 1990 TGME49_chrVIII 4296304 4298540 − ID = TGME49_271892; 3640 length = 2236 TGME49_chrVIII 3611438 3613139 + ID = TGME49_273280; 3641 length = 1701 TGME49_chrV 2172830 2174806 + ID = TGME49_285840; 3642 length = 1976 TGME49_chrIa 271448 273727 − ID = TGME49_293340; 3643 length = 2279 TGME49_chrVIIb 2660463 2662578 + ID = TGME49_259850; 3644 length = 2115 TGME49_chrVIIb 2924755 2925875 − ID = TGME49_259168; 3645 length = 1120 TGME49_chrXII 6094335 6096858 + ID = TGME49_278440; 3646 length = 2523 TGME49_chrIX 5146130 5146913 − ID = TGME49_304980; 3647 length = 783 TGME49_chrXI 3600688 3604400 − ID = TGME49_313673; 3648 length = 3712 TGME49_chrVIIb 1802206 1804702 − ID = TGME49_261260; 3649 length = 2496 TGME49_chrXI 6116659 6118655 − ID = TGME49_216500; 3650 length = 1996 TGME49_chrXII 1854971 1859523 + ID = TGME49_217470; 3651 length = 4552 TGME49_chrX 293996 296317 − ID = TGME49_228490; 3652 length = 2321 TGME49_chrIX 5318345 5320794 + ID = TGME49_305260; 3653 length = 2449 TGME49_chrVI 2399019 2400763 + ID = TGME49_242900; 3654 length = 1744 TGME49_chrVIIa 1642474 1645461 − ID = TGME49_205080; 3655 length = 2987 TGME49_chrVIII 6123971 6127883 − ID = TGME49_269035; 3656 length = 3912 TGME49_chrV 2543184 2545309 − ID = TGME49_285200; 3657 length = 2125 TGME49_chrXII 4492697 4496623 + ID = TGME49_249365; 3658 length = 3926 TGME49_chrVI 303372 308255 + ID = TGME49_238915; 3659 length = 4883 TGME49_chrII 179710 182938 + ID = TGME49_221260; 3660 length = 3228 TGME49_chrXII 4294888 4296930 − ID = TGME49_249000; 3661 length = 2042 TGME49_chrIX 3505245 3508638 − ID = TGME49_289880; 3662 length = 3393 TGME49_chrVIIb 2869299 2871159 + ID = TGME49_259210; 3663 length = 1860 TGME49_chrVIIa 3777648 3779712 + ID = TGME49_201800; 3664 length = 2064 TGME49_chrXI 3072074 3074339 − ID = TGME49_313055; 3665 length = 2265 TGME49_chrVIIa 4157220 4159151 − ID = TGME49_281500; 3666 length = 1931 TGME49_chrVIIb 57559 61364 − ID = TGME49_264225; 3667 length = 3805 TGME49_chrXI 1876735 1880862 + ID = TGME49_311230; 3668 length = 4127 TGME49_chrVIIb 4440597 4442145 + ID = TGME49_256810; 3669 length = 1548 TGME49_chrVIIa 3072309 3074641 + ID = TGME49_202730; 3670 length = 2332 TGME49_chrVIII 295302 299523 − ID = TGME49_229480; 3671 length = 4221 TGME49_chrXI 3700842 3703550 − ID = TGME49_313800; 3672 length = 2708 TGME49_chrIb 783599 787408 − ID = TGME49_208560; 3673 length = 3809 TGME49_chrVIII 6337954 6339540 + ID = TGME49_268730; 3674 length = 1586 TGME49_chrXI 2630045 2632405 + ID = TGME49_312360; 3675 length = 2360 TGME49_chrIX 1235277 1239596 − ID = TGME49_266300; 3676 length = 4319 TGME49_chrIX 894353 898324 + ID = TGME49_266920; 3677 length = 3971 TGME49_chrVIII 4158964 4160790 + ID = TGME49_272180; 3678 length = 1826 TGME49_chrX 2443820 2448305 + ID = TGME49_225150; 3679 length = 4485 TGME49_chrIa 236822 238568 + ID = TGME49_293290; 3680 length = 1746 TGME49_chrIX 5825997 5827653 + ID = TGME49_306200; 3681 length = 1656 TGME49_chrIX 2354796 2356195 − ID = TGME49_288050; 3682 length = 1399 TGME49_chrVIII 3128353 3129861 − ID = TGME49_273995; 3683 length = 1508 TGME49_chrVIIb 282534 283983 + ID = TGME49_263860; 3684 length = 1449 TGME49_chrV 1285449 1287602 − ID = TGME49_213748; 3685 length = 2153 TGME49_chrIX 4127078 4130241 + ID = TGME49_291120; 3686 length = 3163 TGME49_chrVIII 2747263 2749263 + ID = TGME49_233720; 3687 length = 2000 TGME49_chrXII 3414639 3417680 − ID = TGME49_247550; 3688 length = 3041 TGME49_chrX 6010344 6014213 + ID = TGME49_214080; 3689 length = 3869 TGME49_chrXI 763150 767129 + ID = TGME49_309720; 3690 length = 3979 TGME49_chrVI 118877 121839 + ID = TGME49_238200; 3691 length = 2962 TGME49_chrXI 829867 831550 − ID = TGME49_309810; 3692 length = 1683 TGME49_chrVI 2360228 2365079 − ID = TGME49_242860; 3693 length = 4851 TGME49_chrX 3978545 3981345 + ID = TGME49_212200; 3694 length = 2800 TGME49_chrXII 6852419 6855685 − ID = TGME49_276920; 3695 length = 3266 TGME49_chrVIIb 4943943 4948498 + ID = TGME49_255260; 3696 length = 4555 TGME49_chrXII 4707577 4709680 + ID = TGME49_249650; 3697 length = 2103 TGME49_chrVIIb 4709972 4711447 − ID = TGME49_255710; 3698 length = 1475 TGME49_chrIX 2083440 2086073 − ID = TGME49_264740; 3699 length = 2633 TGME49_chrV 2850906 2853929 − ID = TGME49_284040; 3700 length = 3023 TGME49_chrX 5951513 5954484 − ID = TGME49_237520; 3701 length = 2971 TGME49_chrVIII 5113899 5115543 + ID = TGME49_270630; 3702 length = 1644 TGME49_chrIb 781751 786180 + ID = TGME49_208570; 3703 length = 4429 TGME49_chrX 2377395 2379215 + ID = TGME49_225240; 3704 length = 1820 TGME49_chrX 3134556 3137082 + ID = TGME49_224275; 3705 length = 2526 TGME49_chrV 1005836 1007767 + ID = TGME49_213410; 3706 length = 1931 TGME49_chrXI 3469048 3470899 − ID = TGME49_313540; 3707 length = 1851 TGME49_chrVIII 1049473 1053414 − ID = TGME49_230830; 3708 length = 3941 TGME49_chrVI 3300769 3304052 − ID = TGME49_244470; 3709 length = 3283 TGME49_chrXI 793193 797745 − ID = TGME49_309760; 3710 length = 4552 TGME49_chrXII 736911 739042 − ID = TGME49_219682; 3711 length = 2131 TGME49_chrV 1764292 1768196 + ID = TGME49_286595; 3712 length = 3904 TGME49_chrVI 2678544 2680887 + ID = TGME49_243500; 3713 length = 2343 TGME49_chrVI 2944414 2946280 + ID = TGME49_244000; 3714 length = 1866 TGME49_chrVI 3253287 3255288 + ID = TGME49_244430; 3715 length = 2001 TGME49_chrX 6205595 6210365 + ID = TGME49_214280; 3716 length = 4770 TGME49_chrIX 4037286 4041660 − ID = TGME49_291005; 3717 length = 4374 TGME49_chrIX 4585284 4586943 − ID = TGME49_292160; 3718 length = 1659 TGME49_chrIa 1088361 1093316 + ID = TGME49_294720; 3719 length = 4955 TGME49_chrVIII 2805898 2808434 + ID = TGME49_233810; 3720 length = 2536 TGME49_chrV 860119 861470 + ID = TGME49_213115; 3721 length = 1351 TGME49_chrIa 1560221 1563486 + ID = TGME49_295720; 3722 length = 3265 TGME49_chrIV 2667136 2669610 + ID = TGME49_317720; 3723 length = 2474 TGME49_chrVI 1655341 1658987 + ID = TGME49_241155; 3724 length = 3646 TGME49_chrVIIb 430148 433668 − ID = TGME49_263630; 3725 length = 3520 TGME49_chrIX 4677697 4679657 − ID = TGME49_292300; 3726 length = 1960 TGME49_chrX 3531731 3534835 + ID = TGME49_223845; 3727 length = 3104 TGME49_chrX 6552144 6552859 + ID = TGME49_214860; 3728 length = 715 TGME49_chrVIII 1928635 1933235 + ID = TGME49_232190; 3729 length = 4600 TGME49_chrVIIb 4963848 4965565 + ID = TGME49_255245; 3730 length = 1717 TGME49_chrXI 2272267 2276540 − ID = TGME49_311765; 3731 length = 4273 TGME49_chrXI 3206386 3210859 − ID = TGME49_313235; 3732 length = 4473 TGME49_chrVIII 1149159 1152853 + ID = TGME49_230970; 3733 length = 3694 TGME49_chrII 447679 452475 − ID = TGME49_221570; 3734 length = 4796 TGME49_chrXII 386080 388449 − ID = TGME49_307760; 3735 length = 2369 TGME49_chrVIII 676375 678638 + ID = TGME49_230200; 3736 length = 2263 TGME49_chrXII 3180527 3182528 − ID = TGME49_247220; 3737 length = 2001 TGME49_chrVIII 5945676 5950322 + ID = TGME49_269270; 3738 length = 4646 TGME49_chrVIII 451670 454022 + ID = TGME49_229900; 3739 length = 2352 TGME49_chrXII 2632703 2633950 + ID = TGME49_246060; 3740 length = 1247 TGME49_chrXI 2930147 2932129 − ID = TGME49_312820; 3741 length = 1982 TGME49_chrIX 4590678 4593804 + ID = TGME49_292180; 3742 length = 3126 TGME49_chrV 2650784 2654467 − ID = TGME49_284630; 3743 length = 3683 TGME49_chrX 2024148 2027899 + ID = TGME49_225810; 3744 length = 3751 TGME49_chrVIIa 4226184 4229009 + ID = TGME49_281630; 3745 length = 2825 TGME49_chrXII 4960618 4964965 − ID = TGME49_249960; 3746 length = 4347 TGME49_chrXII 1134635 1136707 − ID = TGME49_219100; 3747 length = 2072 TGME49_chrVIII 684588 686890 − ID = TGME49_230205; 3748 length = 2302 TGME49_chrIV 1209441 1210630 − ID = TGME49_318590; 3749 length = 1189 TGME49_chrVI 2692449 2693266 + ID = TGME49_243520; 3750 length = 817 TGME49_chrV 1838282 1841112 − ID = TGME49_286420; 3751 length = 2830 TGME49_chrVIII 920039 922135 − ID = TGME49_230610; 3752 length = 2096 TGME49_chrX 2698033 2701877 − ID = TGME49_224905; 3753 length = 3844 TGME49_chrXI 2114575 2119619 + ID = TGME49_311485; 3754 length = 5044 TGME49_chrXII 1401285 1403127 + ID = TGME49_218580; 3755 length = 1842 TGME49_chrVIIb 4874138 4879043 − ID = TGME49_255370; 3756 length = 4905 TGME49_chrVIII 4334110 4336235 − ID = TGME49_271860; 3757 length = 2125 TGME49_chrVIII 1955865 1958248 + ID = TGME49_232220; 3758 length = 2383 TGME49_chrVIIa 4058231 4061062 + ID = TGME49_281400; 3759 length = 2831 TGME49_chrXII 5605748 5608371 − ID = TGME49_251830; 3760 length = 2623 TGME49_chrX 7145189 7146960 + ID = TGME49_215750; 3761 length = 1771 TGME49_chrIX 5304271 5305970 − ID = TGME49_305230; 3762 length = 1699 TGME49_chrIb 1709895 1713439 + ID = TGME49_321600; 3763 length = 3544 TGME49_chrXII 5667819 5669852 − ID = TGME49_251920; 3764 length = 2033 TGME49_chrXI 1032945 1037980 − ID = TGME49_310050; 3765 length = 5035 TGME49_chrXI 5106537 5108324 − ID = TGME49_315958; 3766 length = 1787 TGME49_chrVIIb 1117766 1121043 − ID = TGME49_262630; 3767 length = 3277 TGME49_chrIb 772266 774883 + ID = TGME49_208550; 3768 length = 2617 TGME49_chrIb 627070 629071 − ID = TGME49_208350; 3769 length = 2001 TGME49_chrX 6319660 6321243 + ID = TGME49_214500; 3770 length = 1583 TGME49_chrVIIb 2192639 2196472 − ID = TGME49_260520; 3771 length = 3833 TGME49_chrVI 898593 901403 − ID = TGME49_239755; 3772 length = 2810 TGME49_chrXI 4168642 4173147 + ID = TGME49_314530; 3773 length = 4505 TGME49_chrIa 111718 114297 − ID = TGME49_293050; 3774 length = 2579 TGME49_chrXII 2783691 2785982 − ID = TGME49_246450; 3775 length = 2291 TGME49_chrXI 1288133 1292845 − ID = TGME49_310350; 3776 length = 4712 TGME49_chrXII 162730 165254 − ID = TGME49_300200; 3777 length = 2524 TGME49_chrIX 3575960 3579143 − ID = TGME49_290000; 3778 length = 3183 TGME49_chrXII 3356485 3359532 + ID = TGME49_247470; 3779 length = 3047 TGME49_chrVIII 2112448 2113740 + ID = TGME49_232460; 3780 length = 1292 TGME49_chrVIIa 3520331 3522747 − ID = TGME49_202210; 3781 length = 2416 TGME49_chrVIIb 1807507 1811746 − ID = TGME49_261250; 3782 length = 4239 TGME49_chrVIIb 1326486 1331064 − ID = TGME49_262170; 3783 length = 4578 TGME49_chrXII 4742982 4745450 + ID = TGME49_249702; 3784 length = 2468 TGME49_chrV 2699767 2701801 + ID = TGME49_284580; 3785 length = 2034 TGME49_chrXI 2716805 2718646 + ID = TGME49_312480; 3786 length = 1841 TGME49_chrIX 772823 775776 − ID = TGME49_267110; 3787 length = 2953 TGME49_chrVI 1683551 1687309 + ID = TGME49_241240; 3788 length = 3758 TGME49_chrIV 1708862 1710770 + ID = TGME49_211440; 3789 length = 1908 TGME49_chrVIIb 2348892 2350447 + ID = TGME49_260325; 3790 length = 1555 TGME49_chrX 1012359 1015635 + ID = TGME49_227335; 3791 length = 3276 TGME49_chrX 6603260 6606386 − ID = TGME49_214930; 3792 length = 3126 TGME49_chrVIII 434978 437027 + ID = TGME49_229780; 3793 length = 2049 TGME49_chrVIII 1536361 1538858 − ID = TGME49_231780; 3794 length = 2497 TGME49_chrVI 890233 892412 + ID = TGME49_239752; 3795 length = 2179 TGME49_chrX 775064 778810 + ID = TGME49_227840; 3796 length = 3746 TGME49_chrVIII 5128576 5133324 − ID = TGME49_270620; 3797 length = 4748 TGME49_chrV 1696352 1699779 + ID = TGME49_286740; 3798 length = 3427 TGME49_chrIX 4570167 4571563 − ID = TGME49_292130; 3799 length = 1396 TGME49_chrIb 1506997 1508664 − ID = TGME49_209870; 3800 length = 1667 TGME49_chrXI 5888682 5890417 − ID = TGME49_216785; 3801 length = 1735 TGME49_chrXI 216523 219848 + ID = TGME49_306870; 3802 length = 3325 TGME49_chrVIIa 3745951 3750483 − ID = TGME49_201850; 3803 length = 4532 TGME49_chrXII 5911846 5916676 − ID = TGME49_278740; 3804 length = 4830 TGME49_chrVIIb 3025423 3026890 − ID = TGME49_259020; 3805 length = 1467 TGME49_chrXI 1475654 1480111 − ID = TGME49_310610; 3806 length = 4457 TGME49_chrXII 5760821 5764702 + ID = TGME49_278910; 3807 length = 3881 TGME49_chrIX 5163063 5165571 − ID = TGME49_305010; 3808 length = 2508 TGME49_chrIa 808274 811964 + ID = TGME49_294340; 3809 length = 3690 TGME49_chrXII 425609 430368 − ID = TGME49_307810; 3810 length = 4759 TGME49_chrIX 189607 191648 − ID = TGME49_279430; 3811 length = 2041 TGME49_chrXII 6699406 6704060 − ID = TGME49_277240; 3812 length = 4654 TGME49_chrX 3862116 3866423 + ID = TGME49_223390; 3813 length = 4307 TGME49_chrIb 163682 165355 − ID = TGME49_207620; 3814 length = 1673 TGME49_chrVIIb 628606 632828 − ID = TGME49_263330; 3815 length = 4222 TGME49_chrVIII 4276676 4280983 − ID = TGME49_271935; 3816 length = 4307 TGME49_chrV 1151826 1153503 + ID = TGME49_213580; 3817 length = 1677 TGME49_chrIX 3597344 3600415 − ID = TGME49_290030; 3818 length = 3071 TGME49_chrVIIa 1207940 1209729 + ID = TGME49_205700; 3819 length = 1789 TGME49_chrXII 1716091 1718180 − ID = TGME49_218192; 3820 length = 2089 TGME49_chrVI 1072208 1074913 + ID = TGME49_240220; 3821 length = 2705 TGME49_chrIX 3344898 3346813 + ID = TGME49_289615; 3822 length = 1915 TGME49_chrXII 193234 197614 − ID = TGME49_300130; 3823 length = 4380 TGME49_chrIX 5678742 5680658 − ID = TGME49_305930; 3824 length = 1916 TGME49_chrIa 511367 514250 + ID = TGME49_293700; 3825 length = 2883 TGME49_chrXI 3234644 3236534 + ID = TGME49_313280; 3826 length = 1890 TGME49_chrIa 1342885 1345816 − ID = TGME49_295035; 3827 length = 2931 TGME49_chrIX 476754 479709 + ID = TGME49_267660; 3828 length = 2955 TGME49_chrXII 5454860 5457281 − ID = TGME49_251550; 3829 length = 2421 TGME49_chrX 6552144 6556896 + ID = TGME49_214870; 3830 length = 4752 TGME49_chrVIIa 3180348 3184059 + ID = TGME49_202590; 3831 length = 3711 TGME49_chrIX 5280883 5283665 − ID = TGME49_305190; 3832 length = 2782 TGME49_chrX 3701807 3706821 − ID = TGME49_223610; 3833 length = 5014 TGME49_chrVIII 4742918 4744434 − ID = TGME49_271070; 3834 length = 1516 TGME49_chrX 6329257 6330831 − ID = TGME49_214510; 3835 length = 1574 TGME49_chrVIIb 4135277 4137872 + ID = TGME49_257300; 3836 length = 2595 TGME49_chrVIIb 3296604 3298791 − ID = TGME49_258630; 3837 length = 2187 TGME49_chrVIII 2597579 2599382 − ID = TGME49_233330; 3838 length = 1803 TGME49_chrX 551024 552313 + ID = TGME49_228140; 3839 length = 1289 TGME49_chrIX 4614733 4617149 + ID = TGME49_292220; 3840 length = 2416 TGME49_chrIV 110065 114937 + ID = TGME49_320720; 3841 length = 4872 TGME49_chrIX 3383102 3384808 − ID = TGME49_289690; 3842 length = 1706 TGME49_chrXI 3166849 3168996 + ID = TGME49_313200; 3843 length = 2147 TGME49_chrVIII 1658293 1660173 + ID = TGME49_231940; 3844 length = 1880 TGME49_chrXI 749160 751293 + ID = TGME49_309600; 3845 length = 2133 TGME49_chrX 5340571 5342425 − ID = TGME49_236220; 3846 length = 1854 TGME49_chrIX 4109881 4114158 − ID = TGME49_291080; 3847 length = 4277 TGME49_chrVIIb 579048 580735 − ID = TGME49_263410; 3848 length = 1687 TGME49_chrIb 1354758 1356812 − ID = TGME49_209585; 3849 length = 2054 TGME49_chrII 114763 116965 − ID = TGME49_221180; 3850 length = 2202 TGME49_chrX 7457352 7459980 + ID = TGME49_207240; 3851 length = 2628 TGME49_chrXI 3622165 3624128 + ID = TGME49_313700; 3852 length = 1963 TGME49_chrXI 4594911 4596494 + ID = TGME49_315240; 3853 length = 1583 TGME49_chrVIIa 3667870 3670309 − ID = TGME49_202050; 3854 length = 2439 TGME49_chrVIII 3750977 3753691 − ID = TGME49_272760; 3855 length = 2714 TGME49_chrV 2731928 2734972 − ID = TGME49_284540; 3856 length = 3044 TGME49_chrIX 5312955 5315417 + ID = TGME49_305250; 3857 length = 2462 TGME49_chrVIII 1242184 1246962 + ID = TGME49_231120; 3858 length = 4778 TGME49_chrII 1270561 1272652 + ID = TGME49_222870; 3859 length = 2091 TGME49_chrIa 1394581 1398592 + ID = TGME49_295100; 3860 length = 4011 TGME49_chrII 695109 697038 + ID = TGME49_221922; 3861 length = 1929 TGME49_chrIV 231725 234333 + ID = TGME49_320588; 3862 length = 2608 TGME49_chrXII 473177 474441 + ID = TGME49_307980; 3863 length = 1264 TGME49_chrVIIb 3849337 3852143 + ID = TGME49_257755; 3864 length = 2806 TGME49_chrVIIa 1664628 1666761 − ID = TGME49_205040; 3865 length = 2133 TGME49_chrVIIb 3685950 3689788 + ID = TGME49_257970; 3866 length = 3838 TGME49_chrX 1921524 1925824 + ID = TGME49_225930; 3867 length = 4300 TGME49_chrX 7302683 7304952 − ID = TGME49_275480; 3868 length = 2269 TGME49_chrIX 2710220 2712817 + ID = TGME49_288730; 3869 length = 2597 TGME49_chrVIIb 3551916 3554846 − ID = TGME49_258150; 3870 length = 2930 TGME49_chrXII 3395404 3397801 − ID = TGME49_247530; 3871 length = 2397 TGME49_chrXII 2036318 2041237 − ID = TGME49_217710; 3872 length = 4919 TGME49_chrVIII 6601085 6602909 − ID = TGME49_268260; 3873 length = 1824 TGME49_chrVIIb 2477511 2479458 − ID = TGME49_260180; 3874 length = 1947 TGME49_chrXII 847627 848796 + ID = TGME49_219580; 3875 length = 1169 TGME49_chrXI 5245329 5247973 + ID = TGME49_316340; 3876 length = 2644 TGME49_chrVIII 1595952 1597448 − ID = TGME49_231865; 3877 length = 1496 TGME49_chrX 4882399 4885373 − ID = TGME49_235460; 3878 length = 2974 TGME49_chrXII 1510400 1513768 + ID = TGME49_218470; 3879 length = 3368 TGME49_chrXII 1275377 1278904 + ID = TGME49_218820; 3880 length = 3527 TGME49_chrIX 4321869 4323613 − ID = TGME49_291670; 3881 length = 1744 TGME49_chrIX 1600603 1603702 + ID = TGME49_265370; 3882 length = 3099 TGME49_chrXII 2166215 2167918 − ID = TGME49_217830; 3883 length = 1703 TGME49_chrIV 1694292 1697186 + ID = TGME49_211460; 3884 length = 2894 TGME49_chrX 6884604 6886087 + ID = TGME49_215300; 3885 length = 1483 TGME49_chrXI 4030644 4031150 − ID = TGME49_314350; 3886 length = 506 TGME49_chrXI 5713685 5715292 − ID = TGME49_217030; 3887 length = 1607 TGME49_chrVIIa 3187548 3190806 + ID = TGME49_202580; 3888 length = 3258 TGME49_chrIX 1479516 1483804 + ID = TGME49_265650; 3889 length = 4288 TGME49_chrXII 1108042 1109700 + ID = TGME49_219140; 3890 length = 1658 TGME49_chrIa 144640 149293 − ID = TGME49_293180; 3891 length = 4653 TGME49_chrVIIa 3402771 3404549 + ID = TGME49_202350; 3892 length = 1778 TGME49_chrV 1107121 1109027 + ID = TGME49_213500; 3893 length = 1906 TGME49_chrV 1652865 1655496 + ID = TGME49_286800; 3894 length = 2631 TGME49_chrX 6732035 6733904 − ID = TGME49_215070; 3895 length = 1869 TGME49_chrVIII 3331943 3336912 + ID = TGME49_273650; 3896 length = 4969 TGME49_chrXII 6757204 6757912 − ID = TGME49_277055; 3897 length = 708 TGME49_chrXI 4086745 4089078 − ID = TGME49_314415; 3898 length = 2333 TGME49_chrVIIb 228036 231382 + ID = TGME49_264020; 3899 length = 3346 TGME49_chrVIIa 4227427 4230194 − ID = TGME49_281620; 3900 length = 2767 TGME49_chrV 1874807 1879170 + ID = TGME49_286260; 3901 length = 4363 TGME49_chrVI 3027874 3029432 + ID = TGME49_244110; 3902 length = 1558 TGME49_chrIV 1709601 1711557 − ID = TGME49_211450; 3903 length = 1956 TGME49_chrXII 2220861 2225036 + ID = TGME49_217915; 3904 length = 4175 TGME49_chrXI 828620 830503 + ID = TGME49_309820; 3905 length = 1883 TGME49_chrVIII 5192539 5195213 + ID = TGME49_270550; 3906 length = 2674 TGME49_chrX 6927629 6929143 + ID = TGME49_215370; 3907 length = 1514 TGME49_chrXI 5224384 5226744 + ID = TGME49_316300; 3908 length = 2360 TGME49_chrVI 2959203 2963259 − ID = TGME49_244010; 3909 length = 4056 TGME49_chrXI 5774652 5776514 + ID = TGME49_216950; 3910 length = 1862 TGME49_chrIa 1804411 1808455 + ID = TGME49_295360; 3911 length = 4044 TGME49_chrVI 1021188 1023814 + ID = TGME49_240050; 3912 length = 2626 TGME49_chrIa 184672 186967 + ID = TGME49_293240; 3913 length = 2295 TGME49_chrVIIb 1578553 1580579 − ID = TGME49_261690; 3914 length = 2026 TGME49_chrXI 1557851 1562530 + ID = TGME49_310740; 3915 length = 4679 TGME49_chrX 3314815 3319616 − ID = TGME49_224130; 3916 length = 4801 TGME49_chrXII 4563657 4568429 + ID = TGME49_249480; 3917 length = 4772 TGME49_chrIb 1032466 1034841 + ID = TGME49_209090; 3918 length = 2375 TGME49_chrVI 2534155 2537835 − ID = TGME49_243298; 3919 length = 3680 TGME49_chrX 3597511 3600273 + ID = TGME49_223770; 3920 length = 2762 TGME49_chrXII 2678206 2682410 − ID = TGME49_246120; 3921 length = 4204 TGME49_chrIX 4818578 4819481 − ID = TGME49_210400; 3922 length = 903 TGME49_chrXI 2316523 2321340 − ID = TGME49_311840; 3923 length = 4817 TGME49_chrIV 2420083 2421297 − ID = TGME49_301370; 3924 length = 1214 TGME49_chrIV 1822182 1826088 − ID = TGME49_211340; 3925 length = 3906 TGME49_chrXII 3764475 3766489 + ID = TGME49_248260; 3926 length = 2014 TGME49_chrVIII 1207669 1210044 − ID = TGME49_231030; 3927 length = 2375 TGME49_chrX 6868549 6871573 + ID = TGME49_215280; 3928 length = 3024 TGME49_chrVIIb 1643729 1645825 + ID = TGME49_261590; 3929 length = 2096 TGME49_chrXI 1624852 1625815 − ID = TGME49_310840; 3930 length = 963 TGME49_chrXII 269284 271834 − ID = TGME49_300030; 3931 length = 2550 TGME49_chrIX 3914323 3919217 + ID = TGME49_290890; 3932 length = 4894 TGME49_chrVIII 3498835 3500944 − ID = TGME49_273460; 3933 length = 2109 TGME49_chrXI 3267474 3271294 + ID = TGME49_313322; 3934 length = 3820 TGME49_chrX 1135303 1139273 − ID = TGME49_227020; 3935 length = 3970 TGME49_chrVIIa 2000440 2005367 − ID = TGME49_204100; 3936 length = 4927 TGME49_chrX 2136745 2141573 − ID = TGME49_225590; 3937 length = 4828 TGME49_chrIa 497577 499864 + ID = TGME49_293670; 3938 length = 2287 TGME49_chrIX 2730465 2732515 − ID = TGME49_288770; 3939 length = 2050 TGME49_chrXI 6095645 6097770 + ID = TGME49_216510; 3940 length = 2125 TGME49_chrVIII 6110637 6114023 − ID = TGME49_269050; 3941 length = 3386 TGME49_chrV 2296305 2301022 + ID = TGME49_285660; 3942 length = 4717 TGME49_chrIb 1593481 1595867 + ID = TGME49_209970; 3943 length = 2386 TGME49_chrVIIb 917523 919993 − ID = TGME49_262933; 3944 length = 2470 TGME49_chrVIIa 3567094 3568251 − ID = TGME49_202170; 3945 length = 1157 TGME49_chrVI 1302262 1303984 + ID = TGME49_240520; 3946 length = 1722 TGME49_chrXI 6376445 6376951 + ID = TGME49_216150; 3947 length = 506 TGME49_chrIV 1387512 1390320 − ID = TGME49_318370; 3948 length = 2808 TGME49_chrVIII 1248684 1250326 + ID = TGME49_231125; 3949 length = 1642 TGME49_chrIX 1805400 1807228 − ID = TGME49_265080; 3950 length = 1828 TGME49_chrIX 3677519 3678219 + ID = TGME49_290280; 3951 length = 700 TGME49_chrII 1020449 1025166 − ID = TGME49_222300; 3952 length = 4717 TGME49_chrX 912303 916274 + ID = TGME49_227560; 3953 length = 3971 TGME49_chrXI 5699102 5701538 + ID = TGME49_217050; 3954 length = 2436 TGME49_chrIX 211482 214977 + ID = TGME49_279380; 3955 length = 3495 TGME49_chrVIII 5960219 5963166 − ID = TGME49_269260; 3956 length = 2947 TGME49_chrXII 1341036 1345114 − ID = TGME49_218740; 3957 length = 4078 TGME49_chrX 5989380 5991089 − ID = TGME49_237560; 3958 length = 1709 TGME49_chrIV 481795 483580 + ID = TGME49_320120; 3959 length = 1785 TGME49_chrVIII 3598010 3600888 − ID = TGME49_273320; 3960 length = 2878 TGME49_chrIX 3065937 3068225 − ID = TGME49_289190; 3961 length = 2288 TGME49_chrX 1873929 1876445 + ID = TGME49_225990; 3962 length = 2516 TGME49_chrXII 3889205 3891343 + ID = TGME49_248500; 3963 length = 2138 TGME49_chrXII 3445460 3446440 + ID = TGME49_247620; 3964 length = 980 TGME49_chrX 713964 716364 + ID = TGME49_227948; 3965 length = 2400 TGME49_chrX 7423562 7425356 + ID = TGME49_207170; 3966 length = 1794 TGME49_chrV 1716156 1718652 − ID = TGME49_286710; 3967 length = 2496 TGME49_chrV 1238094 1240156 − ID = TGME49_213680; 3968 length = 2062 TGME49_chrIb 1132036 1134997 + ID = TGME49_209230; 3969 length = 2961 TGME49_chrX 5892850 5895594 − ID = TGME49_237460; 3970 length = 2744 TGME49_chrIX 1635792 1638798 − ID = TGME49_265280; 3971 length = 3006 TGME49_chrII 2193632 2198046 + ID = TGME49_298020; 3972 length = 4414 TGME49_chrVIIb 4584305 4588201 + ID = TGME49_255970; 3973 length = 3896 TGME49_chrXII 4413869 4418183 − ID = TGME49_249260; 3974 length = 4314 TGME49_chrXII 1375295 1377205 − ID = TGME49_218610; 3975 length = 1910 TGME49_chrII 2159735 2161907 − ID = TGME49_297990; 3976 length = 2172 TGME49_chrVI 3390012 3392557 − ID = TGME49_244600; 3977 length = 2545 TGME49_chrIX 2379675 2384376 − ID = TGME49_288190; 3978 length = 4701 TGME49_chrIX 5721253 5723275 + ID = TGME49_306010; 3979 length = 2022 TGME49_chrXI 1588995 1592976 + ID = TGME49_310790; 3980 length = 3981 TGME49_chrII 1526942 1530423 − ID = TGME49_297090; 3981 length = 3481 TGME49_chrIV 212060 214189 + ID = TGME49_320592; 3982 length = 2129 TGME49_chrIX 302614 305702 − ID = TGME49_267875; 3983 length = 3088 TGME49_chrX 6964191 6968709 − ID = TGME49_215440; 3984 length = 4518 TGME49_chrXI 3138372 3140384 − ID = TGME49_313140; 3985 length = 2012 TGME49_chrVIIb 305794 307179 − ID = TGME49_263830; 3986 length = 1385 TGME49_chrXII 249631 253074 − ID = TGME49_300048; 3987 length = 3443 TGME49_chrVIIb 4653479 4655650 − ID = TGME49_255890; 3988 length = 2171 TGME49_chrVIIb 1873350 1875365 + ID = TGME49_261075; 3989 length = 2015 TGME49_chrX 5306045 5308393 + ID = TGME49_236158; 3990 length = 2348 TGME49_chrIa 780454 781800 + ID = TGME49_294285; 3991 length = 1346 TGME49_chrVIIa 2946359 2947823 + ID = TGME49_202910; 3992 length = 1464 TGME49_chrXII 3857367 3862038 − ID = TGME49_248445; 3993 length = 4671 TGME49_chrIb 1450314 1452140 + ID = TGME49_209790; 3994 length = 1826 TGME49_chrXII 2082658 2086018 + ID = TGME49_217740; 3995 length = 3360 TGME49_chrVI 3028353 3030855 − ID = TGME49_244100; 3996 length = 2502 TGME49_chrXI 2970744 2973324 + ID = TGME49_312905; 3997 length = 2580 TGME49_chrIb 1210143 1211342 − ID = TGME49_209420; 3998 length = 1199 TGME49_chrVIII 225120 227610 + ID = TGME49_229390; 3999 length = 2490 TGME49_chrVIII 2354860 2357994 − ID = TGME49_233030; 4000 length = 3134 TGME49_chrVIII 3259418 3261475 + ID = TGME49_273790; 4001 length = 2057 TGME49_chrX 1752272 1756039 + ID = TGME49_226260; 4002 length = 3767 TGME49_chrXI 5923228 5926772 + ID = TGME49_216740; 4003 length = 3544 TGME49_chrVIIb 4131702 4133633 + ID = TGME49_257310; 4004 length = 1931 TGME49_chrVIIa 1169485 1173218 + ID = TGME49_205750; 4005 length = 3733 TGME49_chrVIIb 255202 259201 − ID = TGME49_263990; 4006 length = 3999 TGME49_chrIV 1230510 1233030 − ID = TGME49_318560; 4007 length = 2520 TGME49_chrVIIb 1618717 1621489 − ID = TGME49_261650; 4008 length = 2772 TGME49_chrV 3151111 3154171 + ID = TGME49_283450; 4009 length = 3060 TGME49_chrVIII 5745993 5747995 + ID = TGME49_269600; 4010 length = 2002 TGME49_chrVIIb 1719667 1720796 − ID = TGME49_261480; 4011 length = 1129 TGME49_chrVIIa 489530 490382 + ID = TGME49_280375; 4012 length = 852 TGME49_chrVIII 3141675 3145631 − ID = TGME49_273970; 4013 length = 3956 TGME49_chrXI 5516873 5518970 + ID = TGME49_316710; 4014 length = 2097 TGME49_chrIa 1508323 1512231 − ID = TGME49_295850; 4015 length = 3908 TGME49_chrX 4338721 4343260 − ID = TGME49_234400; 4016 length = 4539 TGME49_chrX 309061 312804 + ID = TGME49_228430; 4017 length = 3743 TGME49_chrIb 8721 12586 − ID = TGME49_207365; 4018 length = 3865 TGME49_chrX 6251950 6254576 + ID = TGME49_214340; 4019 length = 2626 TGME49_chrVIII 739200 742279 − ID = TGME49_230380; 4020 length = 3079 TGME49_chrX 1570278 1574363 + ID = TGME49_226500; 4021 length = 4085 TGME49_chrX 681974 683378 + ID = TGME49_227990; 4022 length = 1404 TGME49_chrXI 6467604 6468954 + ID = TGME49_216010; 4023 length = 1350 TGME49_chrVIIa 3933627 3938631 + ID = TGME49_201250; 4024 length = 5004 TGME49_chrVIIa 3007574 3010494 − ID = TGME49_202830; 4025 length = 2920 TGME49_chrX 3256800 3258378 − ID = TGME49_224200; 4026 length = 1578 TGME49_chrXI 4639183 4641514 − ID = TGME49_315300; 4027 length = 2331 TGME49_chrVI 1947456 1949773 + ID = TGME49_242300; 4028 length = 2317 TGME49_chrXII 4726342 4728931 + ID = TGME49_249680; 4029 length = 2589 TGME49_chrVIIb 2488617 2490012 − ID = TGME49_260170; 4030 length = 1395 Table 1. Provided are non-limiting examples of endogenous promoters which can be used along with the construct(s) of some embodiments of the invention. The predicted promoter sequences were obtained based on histone marks data around the genes.

Table 2 lists suitable constitutive and inducible promoters which can be cloned into the nucleic acid construct of some embodiments of the invention.

TABLE 2 constitutive and inducible promoters promoter promoter name mode SEQ ID NO: 5RT70 constitutive promoter 4031 DHFR constitutive promoter 4032 MIC2 constitutive promoter 4033 MIC8 constitutive promoter 4034 SAG1 constitutive promoter 4035 TetO7SAGl inducible promoter 4036 TetO7SAG4 inducible promoter 4037 TUB1 constitutive promoter 4038 TUB8 constitutive promoter 4039 Table 2.

As mentioned, the heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein.

As used herein the phrase “Toxoplasma secreted protein” refers to at least a functional fragment (amino acid sequence) of a Toxoplasma polypeptide which is sufficient in order to be secreted to a host cell when infected in-vitro by the Toxoplasma.

According to some embodiments of the invention, the Toxoplasma secreted protein or the functional fragment thereof is capable of being secreted to a host cell when infected in-vivo by the Toxoplasma.

According to some embodiments of the invention, the first nucleic acid sequence encoding a functional fragment of the Toxoplasma secreted protein.

According to some embodiments of the invention, the first nucleic acid sequence encoding the full-length open reading frame (ORF) of the Toxoplasma secreted protein.

According to some embodiments of the invention, the Toxoplasma secreted protein is secreted from a rhoptry of the Toxoplasma.

According to some embodiments of the invention, the Toxoplasma secreted protein which is secreted from the rhoptry comprises Toxofilin and/or ROP1.

According to some embodiments of the invention, the Toxoplasma secreted protein which is secreted from the rhoptry comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:344-465.

According to some embodiments of the invention, the Toxoplasma secreted protein is a non-rhoptry protein.

According to some embodiments of the invention, the Toxoplasma secreted protein is selected from the group consisting of a microneme protein and a dense granule protein.

According to some embodiments of the invention, the Toxoplasma secreted protein is secreted from a dense granule of the Toxoplasma.

According to some embodiments of the invention, the Toxoplasma secreted protein which is secreted from the dense granule comprises a GRA16, and/or GRA24.

According to some embodiments of the invention, the Toxoplasma secreted protein is secreted from a microneme of the Toxoplasma.

According to some embodiments of the invention, the protein secreted from the microneme comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:280-322.

According to some embodiments of the invention, the protein secreted from the dense granule comprises the amino acid sequence selected from the group consisting of SEQ ID NOs:234-279.

According to some embodiments of the invention, the Toxoplasma secreted protein comprises Toxoplasma gondii macrophage migration inhibitory factor (TgMIF).

Table 3 below lists Toxoplasma-secreted proteins which can be cloned into the nucleic acid construct of some embodiments of the invention, organized according to the organelle to which the protein is localized or predicted to be localized to.

TABLE 3 Toxoplasma proteins Polyn. Polyp. SEQ SEQ Gene ID Gene Product Description Organism organelle ID ID TGME49_289620 cathepsin CPC1 (CPC1) T. gondii Dense 1 234 ME49 Granules TGME49_276130 cathepsin CPC2 (CPC2) T. gondii Dense 2 235 ME49 Granules TGME49_268900 dense granular protein GRA10 T. gondii Dense 3 236 (GRA10) ME49 Granules TGME49_297880 dense granule protein DG32 T. gondii Dense 4 237 ME49 Granules TGME49_270250 dense granule protein GRA1 T. gondii Dense 5 238 (GRA1) ME49 Granules TGME49_212410 dense granule protein GRA11 T. gondii Dense 6 239 ME49 Granules TGME49_237800 dense granule protein GRA11 T. gondii Dense 7 240 ME49 Granules TGME49_275850 dense granule protein GRA12 T. gondii Dense 8 241 (GRA12) ME49 Granules TGME49_288650 dense granule protein GRA12 T. gondii Dense 9 242 (GRA12) ME49 Granules TGME49_239740 dense granule protein GRA14 T. gondii Dense 10 243 (GRAM) ME49 Granules TGME49_275470 dense granule protein GRAI5 T. gondii Dense 11 244 (GRAM) ME49 Granules TGME49_227620 dense granule protein GRA2 T. gondii Dense 12 245 (GRA2) ME49 Granules TGME49_227280 dense granule protein GRA3 T. gondii Dense 13 246 (GRA3) ME49 Granules TGME49_310780 dense granule protein GRA4 T. gondii Dense 14 247 (GRA4) ME49 Granules TGME49_286450 dense granule protein GRA5 T. gondii Dense 15 248 (GRA5) ME49 Granules TGME49_275440 dense granule protein GRA6 T. gondii Dense 16 249 (GRA6) ME49 Granules TGME49_203310 dense granule protein GRA7 T. gondii Dense 17 250 (GRA7) ME49 Granules TGME49_254720 dense granule protein GRA8 T. gondii Dense 18 251 (GRA8) ME49 Granules TGME49_251540 dense granule protein GRA9 T. gondii Dense 19 252 (GRA9) ME49 Granules TGME49_222170 dense-granule antigen DG32 T. gondii Dense 20 253 ME49 Granules TGME49_208830 GRAM T. gondii Dense 21 254 ME49 Granules TGME49_200010 GRA20 T. gondii Dense 22 255 ME49 Granules TGME49_241610 GRA21 T. gondii Dense 23 256 ME49 Granules TGME49_230180 GRA24 T. gondii Dense 24 257 ME49 Granules TGME49_290700 GRA25 T. gondii Dense 25 258 ME49 Granules TGME49_231960 GRA28 T. gondii Dense 26 259 ME49 Granules TGME49_269690 GRA29 T. gondii Dense 27 260 ME49 Granules TGME49_232000 GRA30 T. gondii Dense 28 261 ME49 Granules TGME49_220240 GRA31 T. gondii Dense 29 262 ME49 Granules TGME49_212300 GRA32 T. gondii Dense 30 263 ME49 Granules TGME49_247440 GRA33 T. gondii Dense 31 264 ME49 Granules TGME49_226380 GRA35 T. gondii Dense 32 265 ME49 Granules TGME49_213067 GRA36 T. gondii Dense 33 266 ME49 Granules TGME49_236890 GRA37 T. gondii Dense 34 267 ME49 Granules TGME49_312420 GRA38 T. gondii Dense 35 268 ME49 Granules TGME49_289380 GRA39 T. gondii Dense 36 269 ME49 Granules TGME49_219810 GRA40 T. gondii Dense 37 270 ME49 Granules TGME49_200360 hypothetical protein T. gondii Dense 38 271 ME49 Granules TGME49_203290 hypothetical protein T. gondii Dense 39 272 ME49 Granules TGME49_310790 hypothetical protein T. gondii Dense 40 273 ME49 Granules TGME49_277240 NTPase I T. gondii Dense 41 274 ME49 Granules TGME49_277270 NTPase II T. gondii Dense 42 275 ME49 Granules TGME49_217430 protease inhibitor PI1 (PI1) T. gondii Dense 43 276 ME49 Granules TGME49_208450 protease inhibitor PI2 (PI2) T. gondii Dense 44 277 ME49 Granules TGGT1_411330 putative dense granule protein T. gondii Dense 45 278 GRA11 GT1 Granules TGME49_275860 putative dense granule protein T. gondii Dense 46 279 GRA12 VEG Granules TGME49_261710 ankyrin repeat-containing protein T. gondii Micronemes 47 280 ME49 TGME49_300130 apical membrane antigen 1 domain- T. gondii Micronemes 48 281 containing protein ME49 TGME49_255260 apical membrane antigen AMA1 T. gondii Micronemes 49 282 ME49 TGME49_293770 chitinase-like protein CLP1 (CLP1) T. gondii Micronemes 50 283 ME49 TGME49_204340 GRA34 T. gondii Micronemes 51 284 ME49 TGME49_221480 hypothetical protein T. gondii Micronemes 52 285 ME49 TGME49_289100 MIC18 T. gondii Micronemes 53 286 ME49 TGME49_294790 MIC19 T. gondii Micronemes 54 287 ME49 TGME49_214940 MIC2-associated protein M2AP T. gondii Micronemes 55 288 ME49 TGME49_283540 MIC20 T. gondii Micronemes 56 289 ME49 TGME49_291890 microneme protein MIC1 (MIC1) T. gondii Micronemes 57 290 ME49 TGME49_250710 microneme protein MIC10 (MIC10) T. gondii Micronemes 58 291 ME49 TGME49_204530 microneme protein MIC11 (MIC11) T. gondii Micronemes 59 292 ME49 TGME49_267680 microneme protein MIC12 (MIC12) T. gondii Micronemes 60 293 ME49 TGME49_260190 microneme protein MIC13 (MIC13) T. gondii Micronemes 61 294 ME49 TGME49_218310 microneme protein MIC14 (MIC14) T. gondii Micronemes 62 295 ME49 TGME49_247195 microneme protein MIC15 (MIC15) T. gondii Micronemes 63 296 ME49 TGME49_289630 microneme protein MIC16 (MIC16) T. gondii Micronemes 64 297 ME49 TGME49_200250 microneme protein MIC17A T. gondii Micronemes 65 298 (MIC17A) ME49 TGME49_200240 microneme protein MIC17B T. gondii Micronemes 66 299 (MIC17B) ME49 TGME49_200230 microneme protein MIC17C T. gondii Micronemes 67 300 (MIC17C) ME49 TGME49_201780 microneme protein MIC2 (MIC2) T. gondii Micronemes 68 301 ME49 TGME49_319560 microneme protein MIC3 (MIC3) T. gondii Micronemes 69 302 ME49 TGME49_208030 microneme protein MIC4 (MIC4) T. gondii Micronemes 70 303 ME49 TGME49_277080 microneme protein MIC5 (MIC5) T. gondii Micronemes 71 304 ME49 TGME49_218520 microneme protein MIC6 (MIC6) T. gondii Micronemes 72 305 ME49 TGME49_261780 microneme protein MIC7 (MIC7) T. gondii Micronemes 73 306 ME49 TGME49_245490 microneme protein MIC8 (MIC8) T. gondii Micronemes 74 307 ME49 TGME49_245485 microneme protein MIC9 (MIC9) T. gondii Micronemes 75 308 ME49 TGME49_208730 microneme protein, putative T. gondii Micronemes 76 309 ME49 TGME49_208740 microneme protein, putative T. gondii Micronemes 77 310 ME49 TGME49_254430 microneme protein, putative T. gondii Micronemes 78 311 ME49 TGME49_275798 microneme protein, putative T. gondii Micronemes 79 312 ME49 TGME49_244180 microneme-like protein T. gondii Micronemes 80 313 ME49 TGME49_286740 microneme-like protein T. gondii Micronemes 81 314 ME49 TGME49_200270 PAN/Apple domain-containing T. gondii Micronemes 82 315 protein ME49 TGME49_286150 PAN/Apple domain-containing T. gondii Micronemes 83 316 protein ME49 TGME49_204130 perforin-like protein PLP1 (PLP1) T. gondii Micronemes 84 317 ME49 TGVEG_439620 putative microneme protein T. gondii Micronemes 85 318 VEG TGME49_200290 rhomboid protease R0M1 (R0M1) T. gondii Micronemes 86 319 ME49 TGME49_293900 sporozoite protein with an altered T. gondii Micronemes 87 320 thrombospondin repeat SPATR ME49 TGME49_204050 subtilisin SUB1 (SUB1) T. gondii Micronemes 88 321 ME49 TGME49_206510 toxolysin TLN4 (TLN4) T. gondii Micronemes 89 322 ME49 TGME49_209030 actin ACT1 (ACT1) T. gondii Other 90 323 ME49 TGME49_214290 DJ-1 family protein T. gondii Other 91 324 ME49 TGME49_268850 enolase 2 T. gondii Other 92 325 ME49 TGME49_236040 fructose-1,6-bisphosphate aldolase T. gondii Other 93 326 ME49 TGME49_289690 glyceraldehyde-3-phosphate T. gondii Other 94 327 dehydrogenase GAPDH1 ME49 (GAPDH1) TGME49_290040 macrophage migration inhibitory T. gondii Other 95 328 factor, putative ME49 TGME49_211680 protein disulfide isomerase T. gondii Other 96 329 ME49 TGME49_273610 Secretory phospholipase A2 T. gondii Other 97 330 ME49 TGME49_273620 Secretory phospholipase A2 T. gondii Other 98 331 GT1 TGME49_271570 Toxoplasma gondii family D protein T. gondii Other 99 332 ME49 TGME49_205470 translation elongation factor 2 T. gondii Other 100 333 family protein, putative ME49 TGME49_288360 tryptophanyl-tRNA synthetase T. gondii Other 101 334 (TrpRS2) ME49 TGME49_208590 vacuolar ATP synthase subunit T. gondii Other 102 335 54kD, putative ME49 TGME49_256970 vacuolar ATP synthase subunit A, T. gondii Other 103 336 putative ME49 TGME49_219800 vacuolar ATP synthase subunit b, T. gondii Other 104 337 putative ME49 TGME49_315620 vacuolar ATP synthase subunit C, T. gondii Other 105 338 putative ME49 TGME49_259010 vacuolar ATP synthase subunit d, T. gondii Other 106 339 putative ME49 TGME49_305290 vacuolar atp synthase subunit e, T. gondii Other 107 340 putative ME49 TGME49_310960 vacuolar atp synthase subunit f, T. gondii Other 108 341 putative ME49 TGME49_246560 vacuolar ATP synthase subunit g, T. gondii Other 109 342 putative ME49 TGME49_212310 vacuolar ATP synthetase T. gondii Other 110 343 ME49 TGME49_314250 bradyzoite rhoptry protein BRP1 T. gondii Rhoptries 111 344 (BRP1) ME49 TGME49_209985 cAMP-dependent protein kinase T. gondii Rhoptries 112 345 ME49 TGME49_249670 cathepsin B T. gondii Rhoptries 113 346 ME49 TGME49_252200 cell cycle regulator with zn-finger T. gondii Rhoptries 114 347 domain-containing protein ME49 TGME49_210095 hypothetical protein T. gondii Rhoptries 115 348 ME49 TGME49_296015 hypothetical protein T. gondii Rhoptries 116 349 ME49 TGME49_297070 hypothetical protein T. gondii Rhoptries 117 350 ME49 TGME49_311320 hypothetical protein T. gondii Rhoptries 118 351 ME49 TGME49_321700 hypothetical protein T. gondii Rhoptries 119 352 ME49 TGME49_321710 hypothetical protein T. gondii Rhoptries 120 353 ME49 TGME49_322120 hypothetical protein T. gondii Rhoptries 121 354 ME49 TGME49_323320 hypothetical protein T. gondii Rhoptries 122 355 ME49 TGGT1_410610 hypothetical protein T. gondii Rhoptries 123 356 GT1 TGME49_242118 myosin-light-chain kinase T. gondii Rhoptries 124 357 ME49 TGME49_322000 myosin-light-chain kinase T. gondii Rhoptries 125 358 ME49 TGME49_322010 myosin-light-chain kinase T. gondii Rhoptries 126 359 ME49 TGME49_322100 myosin-light-chain kinase T. gondii Rhoptries 127 360 ME49 TGME49_323300 myosin-light-chain kinase T. gondii Rhoptries 128 361 ME49 TGME49_252500 polo kinase T. gondii Rhoptries 129 362 ME49 TGME49_258225 Predicted rhoptry protein kinase T. gondii Rhoptries 130 363 (ROPK) GT1 TGME49_234950 protein kinase (incomplete catalytic T. gondii Rhoptries 131 364 triad) ME49 TGME49_274170 protein kinase (incomplete catalytic T. gondii Rhoptries 132 365 triad) ME49 TGME49_281675 protein kinase, putative T. gondii Rhoptries 133 366 ME49 TGME49_270320 protein phosphatase 2C domain- T. gondii Rhoptries 134 367 containing protein ME49 TGME49_282055 protein phosphatase PP2C-hn T. gondii Rhoptries 135 368 (PP2CHN) ME49 TGVEG_281675A putative protein kinase T. gondii Rhoptries 136 369 VEG TGVEG_281675B putative protein kinase T. gondii Rhoptries 137 370 VEG TGME49_289680 Ras-related protein Rab11 T. gondii Rhoptries 138 371 ME49 TGGT1_411350 rhoptry kinase family (incomplete T. gondii Rhoptries 139 372 catalytic triad) protein GT1 TGGT1_409600 rhoptry kinase family protein T. gondii Rhoptries 140 373 GT1 TGGT1_411360 rhoptry kinase family protein T. gondii Rhoptries 141 374 GT1 TGVEG_440850 rhoptry kinase family protein T. gondii Rhoptries 142 375 VEG TGVEG_440860 rhoptry kinase family protein T. gondii Rhoptries 143 376 VEG TGVEG_442710 rhoptry kinase family protein T. gondii Rhoptries 144 377 VEG TGME49_308093 rhoptry kinase family protein T. gondii Rhoptries 145 378 (incomplete catalytic triad) ME49 TGME49_308096 rhoptry kinase family protein T. gondii Rhoptries 146 379 (incomplete catalytic triad) ME49 TGME49_227810 rhoptry kinase family protein T. gondii Rhoptries 147 380 ROP11 (incomplete catalytic triad) ME49 (ROP11) TGME49_242240 rhoptry kinase family protein T. gondii Rhoptries 148 381 ROP19A (ROP19A) ME49 TGME49_242250 rhoptry kinase family protein T. gondii Rhoptries 149 382 ROP19B (ROP19B) ME49 TGME49_258230 rhoptry kinase family protein T. gondii Rhoptries 150 383 ROP20 (ROP20) ME49 TGME49_263220 rhoptry kinase family protein T. gondii Rhoptries 151 384 ROP21 (ROP21) ME49 TGME49_207700 rhoptry kinase family protein T. gondii Rhoptries 152 385 ROP22 (incomplete catalytic triad) ME49 (ROP22) TGME49_239600 rhoptry kinase family protein T. gondii Rhoptries 153 386 ROP23 (incomplete catalytic triad) ME49 (ROP23) TGME49_252360 rhoptry kinase family protein T. gondii Rhoptries 154 387 ROP24 (incomplete catalytic triad) ME49 (ROP24) TGME49_202780 rhoptry kinase family protein T. gondii Rhoptries 155 388 ROP25 (ROP25) ME49 TGME49_211260 rhoptry kinase family protein T. gondii Rhoptries 156 389 ROP26 (incomplete catalytic triad) ME49 (ROP26) TGME49_313330 rhoptry kinase family protein T. gondii Rhoptries 157 390 ROP27 (ROP27) ME49 TGME49_258370 rhoptry kinase family protein T. gondii Rhoptries 158 391 ROP28 (ROP28) ME49 TGME49_242230 rhoptry kinase family protein T. gondii Rhoptries 159 392 ROP29 (ROP29) ME49 TGME49_227010 rhoptry kinase family protein T. gondii Rhoptries 160 393 ROP30 (ROP30) ME49 TGME49_258800 rhoptry kinase family protein T. gondii Rhoptries 161 394 ROP31 (ROP31) ME49 TGME49_270920 rhoptry kinase family protein T. gondii Rhoptries 162 395 ROP32 (ROP32) ME49 TGME49_201130 rhoptry kinase family protein T. gondii Rhoptries 163 396 ROP33 (ROP33) ME49 TGME49_240090 rhoptry kinase family protein T. gondii Rhoptries 164 397 ROP34, putative ME49 TGME49_304740 rhoptry kinase family protein T. gondii Rhoptries 165 398 ROP35 (ROP35) ME49 TGME49_207610 rhoptry kinase family protein T. gondii Rhoptries 166 399 ROP36 (incomplete catalytic triad) ME49 (ROP36) TGME49_294560 rhoptry kinase family protein T. gondii Rhoptries 167 400 ROP37 (incomplete catalytic triad) ME49 (ROP37) TGME49_242110 rhoptry kinase family protein T. gondii Rhoptries 168 401 ROP38 (ROP38) ME49 TGME49_262050 rhoptry kinase family protein T. gondii Rhoptries 169 402 ROP39 (ROP39) ME49 TGME49_291960 rhoptry kinase family protein T. gondii Rhoptries 170 403 ROP40 (incomplete catalytic triad) ME49 (ROP40) TGME49_266100 rhoptry kinase family protein T. gondii Rhoptries 171 404 ROP41 (ROP41) ME49 TGME49_230470 rhoptry kinase family protein T. gondii Rhoptries 172 405 ROP46, putative ME49 TGME49_249470 Rhoptry kinase family protein, T. gondii Rhoptries 173 406 truncated (incomplete catalytic ME49 triad) TGME49_253330 Rhoptry kinase family protein, T. gondii Rhoptries 174 407 truncated (incomplete catalytic ME49 triad) TGVEG_322130 rhoptry kinase family ROP19B T. gondii Rhoptries 175 408 VEG TGVEG_269885A rhoptry metalloprotease toxolysin T. gondii Rhoptries 176 409 TLN1 VEG TGVEG_269885B rhoptry metalloprotease toxolysin T. gondii Rhoptries 177 410 TLN1 VEG TGME49_269885 rhoptry metalloprotease toxolysin T. gondii Rhoptries 178 411 TLN1 (TLN1) ME49 TGVEG_310010A rhoptry neck protein RON1 T. gondii Rhoptries 179 412 VEG TGVEG_310010B rhoptry neck protein RON1 T. gondii Rhoptries 180 413 VEG TGME49_310010 rhoptry neck protein RON1 (RON1) T. gondii Rhoptries 181 414 ME49 TGME49_261750 rhoptry neck protein RON10 T. gondii Rhoptries 182 415 (RON10) ME49 TGME49_300100 rhoptry neck protein RON2 (RON2) T. gondii Rhoptries 183 416 ME49 TGME49_223920 rhoptry neck protein RON3 (RON3) T. gondii Rhoptries 184 417 ME49 TGME49_229010 rhoptry neck protein RON4 (RON4) T. gondii Rhoptries 185 418 ME49 TGME49_311470 rhoptry neck protein RON5 (RON5) T. gondii Rhoptries 186 419 ME49 TGVEG_2 rhoptry neck protein RON6 T. gondii Rhoptries 187 420 97960A VEG TGVEG_2 rhoptry neck protein RON6 T. gondii Rhoptries 188 421 97960B VEG TGME49_297960 rhoptry neck protein RON6 (RON6) T. gondii Rhoptries 189 422 ME49 TGME49_306060 rhoptry neck protein RON8 (RON8) T. gondii Rhoptries 190 423 ME49 TGVEG_3 rhoptry neck protein RON9 T. gondii Rhoptries 191 424 08810A VEG TGVEG_3 rhoptry neck protein RON9 T. gondii Rhoptries 192 425 08810B VEG TGME49_308810 rhoptry neck protein RON9 (RON9) T. gondii Rhoptries 193 426 ME49 TGME49_265120 rhoptry neck protein, putative T. gondii Rhoptries 194 427 ME49 TGME49_327200 rhoptry neck protein, putative T. gondii Rhoptries 195 428 ME49 TGME49_309590 rhoptry protein ROP1 (ROP1) T. gondii Rhoptries 196 429 ME49 TGME49_315490 rhoptry protein ROP10 (ROP10) T. gondii Rhoptries 197 430 ME49 TGME49_203990 rhoptry protein ROP12 (ROP12) T. gondii Rhoptries 198 431 ME49 TGME49_312270 rhoptry protein ROP13 (ROP13) T. gondii Rhoptries 199 432 ME49 TGME49_315220 rhoptry protein ROP14 (ROP14) T. gondii Rhoptries 200 433 ME49 TGME49_211290 rhoptry protein ROP15 (ROP15) T. gondii Rhoptries 201 434 ME49 TGME49_262730 rhoptry protein ROP16 (ROP16) T. gondii Rhoptries 202 435 ME49 TGME49_258580 rhoptry protein ROP17 (ROP17) T. gondii Rhoptries 203 436 ME49 TGME49_205250 rhoptry protein ROP18 (ROP18) T. gondii Rhoptries 204 437 ME49 TGME49_215785 rhoptry protein ROP2A (ROP2A) T. gondii Rhoptries 205 438 ME49 TGME49_295125 rhoptry protein ROP4 (ROP4) T. gondii Rhoptries 206 439 ME49 TGGT1_411430 rhoptry protein ROP5 T. gondii Rhoptries 207 440 GT1 TGVEG_442220 rhoptry protein ROP5 T. gondii Rhoptries 208 441 VEG TGME49_308090 rhoptry protein ROP5 (ROP5) T. gondii Rhoptries 209 442 ME49 TGME49_258660 rhoptry protein ROP6 (ROP6) T. gondii Rhoptries 210 443 ME49 TGGT1_365080 rhoptry protein ROP7 T. gondii Rhoptries 211 444 GT1 TGME49_295110 rhoptry protein ROP7 (ROP7) T. gondii Rhoptries 212 445 ME49 TGVEG_363030 rhoptry protein ROP8 T. gondii Rhoptries 213 446 VEG TGME49_215775 rhoptry protein ROP8 (ROP8) T. gondii Rhoptries 214 447 ME49 TGME49_243730 rhoptry protein ROP9 (ROP9) T. gondii Rhoptries 215 448 ME49 TGME49_295105 rhoptry protein, putative T. gondii Rhoptries 216 449 ME49 TGME49_315210 rhoptry protein, putative T. gondii Rhoptries 217 450 ME49 TGME49_315940 rhoptry protein, putative T. gondii Rhoptries 218 451 ME49 TGME49_230350 RON11 T. gondii Rhoptries 219 452 ME49 TGME49_232020 RON12 T. gondii Rhoptries 220 453 ME49 TGME49_294400 RON2L1 T. gondii Rhoptries 221 454 ME49 TGME49_296020 ROP2L11 T. gondii Rhoptries 222 455 VEG TGME49_296000 ROP2L12 T. gondii Rhoptries 223 456 ME49 TGME49_242100 ROP38 T. gondii Rhoptries 224 457 ME49 TGME49_261740 ROP47 T. gondii Rhoptries 225 458 ME49 TGME49_218270 ROP48 T. gondii Rhoptries 226 459 ME49 TGME49_308075 ROP5 T. gondii Rhoptries 227 460 VEG TGME49_241000 ROP51 T. gondii Rhoptries 228 461 ME49 TGME49_210370 ROP54 T. gondii Rhoptries 229 462 ME49 TGME49_300290 SNARE domain-containing protein T. gondii Rhoptries 230 463 ME49 TGME49_299060 sodium/hydrogen exchanger NHE2 T. gondii Rhoptries 231 464 ME49 TGME49_314500 subtilisin SUB2 (SUB2) T. gondii Rhoptries 232 465 ME49 TGME49_214080 toxofilin T. gondii Rhoptries 233 466 ME49 Table 3. “polyn.” = polynucleotide; “polyp” = polypeptide.

According to some embodiments of the invention, the heterologous polynucleotide further comprises a Toxoplasma untranslated region (UTR) nucleic acid sequence.

According to some embodiments of the invention, the Toxoplasma untranslated region (UTR) nucleic acid sequence is upstream and/or downstream of the open reading frame of the heterologous polynucleotide (e.g., which encodes the Toxoplasma secreted protein fused in frame with the pharmaceutical polypeptide).

According to some embodiments of the invention, the Toxoplasma 5′-untranslated region (5′-UTR) is placed upstream of the Toxoplasma secreted protein open reading frame.

According to some embodiments of the invention, the Toxoplasma 3′-untranslated region (3′-UTR) is placed downstream of the open reading frame encoding the Toxoplasma secreted protein fused in frame with the pharmaceutical polypeptide.

According to some embodiments of the invention, the Toxoplasma 3′ untranslated region (3′-UTR) nucleic acid sequence is the GRA2 3′-UTR, GRA16 3′-UTR, GRA24 3′-UTR, SAG1 3′-UTR, or the DHFR 3′-UTR.

According to some embodiments of the invention, the Toxoplasma 5′ untranslated region (5′-UTR) nucleic acid sequence is the GRA2 5′-UTR, GRA16 5′-UTR, GRA24 5′-UTR, SAG1 5′-UTR, or the DHFR 5′-UTR.

According to some embodiments of the invention, the Toxoplasma untranslated region (UTR) nucleic acid sequence is the Toxofilin 3′-UTR.

As mentioned, the heterologous polynucleotide comprises a second nucleic acid sequence encoding a pharmaceutical polypeptide being fused in frame downstream of the Toxoplasma secreted protein.

As used herein the phrase “pharmaceutical polypeptide” refers to a polypeptide having a therapeutic effect, e.g., capable of treating a pathology, when introduced into cell(s) of a subject in need thereof.

It should be noted that for certain diseases, the pharmaceutical polypeptide may be effective when reaching a certain organ, tissue, cell, cell compartment or cellular localization within the subject. For example, for treating a neurological disease, the pharmaceutical composition is preferably targeted to the nervous system, e.g., neurons, glia or other cells. Additionally or alternatively, for certain diseases, the pharmaceutical polypeptide should reach a certain cellular localization such as the cell nucleus in case the target of the pharmaceutical composition is situated (positioned) within the cell nucleus. For example, in the case of MECP2, the active protein binds to DNA within the nucleus and regulates gene expression.

According to some embodiments of the invention, the nucleic acid construct further comprises at least one in frame cleavage site, which allows detachment of the pharmaceutical polypeptide from the Toxoplasma secreted protein.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises a wild type amino acid sequence corresponding to the endogenous protein capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises an antibody capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises an antigen capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises a toxin capable of treating the pathology.

According to some embodiments of the invention, the pharmaceutical polypeptide comprises an enzyme, a structural polypeptide, a motility polypeptide, a regulatory polypeptide, a storage polypeptide, a signaling/ligand polypeptide, a receptor polypeptide, a sensory polypeptide, an antibody, a protein channel and/or a transport polypeptide.

According to some embodiments of the invention, the pharmaceutical polypeptide is Galactocerebrosidase (GALC).

According to some embodiments of the invention, the pharmaceutical polypeptide is Galactocerebrosidase (GALC) isoform 1, isoform 2, isoform 3, isoform 4 or isoform 5.

According to some embodiments of the invention, the pharmaceutical polypeptide is Methyl-CpG Binding Protein 2 (MECP2).

According to some embodiments of the invention, the pharmaceutical polypeptide is Methyl-CpG Binding Protein 2 (MECP2) isoform 1 or MECP2 isoform 2.

According to some embodiments of the invention, the pharmaceutical polypeptide is Glial Cell Derived Neurotrophic Factor (GDNF).

According to some embodiments of the invention, the pharmaceutical polypeptide is Glial Cell Derived Neurotrophic Factor (GDNF) isoform 1, isoform 2, isoform 3, isoform 4 or isoform 5.

According to some embodiments of the invention, the pharmaceutical polypeptide is Aspartoacylase (ASPA).

According to some embodiments of the invention, the pharmaceutical polypeptide is Survival Motor Neuron Protein (SMN1).

According to some embodiments of the invention, the pharmaceutical polypeptide is Survival Motor Neuron Protein isoform SMN, isoform SMN-delta5, isoform SMN-delta7, or isoform SMN-delta57.

According to some embodiments of the invention, the pharmaceutical polypeptide is Parkin (PARK2).

According to some embodiments of the invention, the pharmaceutical polypeptide is Parkin (PARK2) isoform 1, isoform 2, isoform 3, isoform 4, isoform 5, isoform 6, isoform 7, or isoform 8.

According to some embodiments of the invention, the pharmaceutical polypeptide is Transcription Factor EB (TFEB).

According to some embodiments of the invention, the pharmaceutical polypeptide is Transcription Factor EB (TFEB) isoform 1 or isoform 2.

According to some embodiments of the invention, the pharmaceutical polypeptide is a TALEN (TALE nuclease).

According to some embodiments of the invention, the pharmaceutical polypeptide is a TALE TF (TALE transcription factor).

Table 4 hereinbelow, lists exemplary therapeutic proteins, which can be secreted to the subject by the Toxoplasma of some embodiments of the invention.

TABLE 4 exemplary pharmaceutical proteins Polypeptide Polynucleotide GenBank SEQ GenBank SEQ Gene Accession ID Accession Number ID Name/Symbol Number NO: (coding sequence) NO: TFEB NP_001258874.1 4610 NM_001271945.1 4600 TFEB NP_001161299.2 4618 NM_001167827.2 4619 TFEB NP_001258873.1 4620 NM_001271944.1 4621 TFEB NP_009093.1 4622 NM_007162.2 4623 TFEB NP_001258872.1 4624 NM_001271943.1 4625 HGSNAT NP_689632 4301 NM_152419 4040 MEF2C NP_001124477 4302 NM_001131005 4041 MEF2C NP_002388 4303 NM_002397 4042 NRTN NP_004549 4304 NM_004558 4043 PGF NP_002623 4305 NM_002632 4044 RPE65 NP_000320 4306 NM_000329 4045 GDNF NP_000505 4307 NM_000514 4046 GDNF NP_954701 4308 NM_199231 4047 CNGB3 NP_061971 4309 NM_019098 4048 BDNF NP_001137277 4310 NM_001143816 4049 BDNF NP_001137279 4311 NM_001143814 4050 BDNF NP_001137288 4312 NM_001143813 4051 BDNF NP_001137278 4313 NM_001143812 4052 BDNF NP_733931 4314 NM_001143806 4053 BDNF NP_733930 4315 NM_001143811 4054 BDNF NP_733929 4316 NM_001709 4055 BDNF NP_733927 4317 NM_001143805 4056 BDNF NP_733928 4318 NM_001143810 4057 BDNF NP_001700 4319 NM_170735 4058 BDNF NP_001137281 4320 NM_170734 4059 BDNF NP_001137282 4321 NM_170733 4060 BDNF NP_001137280 4322 NM_170732 4061 BDNF NP_001137285 4323 NM_170731 4062 BDNF NP_001137286 4324 NM_001143809 4063 BDNF NP_001137283 4325 NM_001143807 4064 BDNF NP_001137284 4326 NM_001143808 4065 APP NP_001129601 4327 NM_000484 4066 APP NP_958817 4328 NM_201414 4067 APP NP_958816 4329 NM_001136131 4068 APP NP_001129602 4330 NM_201413 4069 APP NP_001129488 4331 NM_001136130 4070 APP NP_000475 4332 NM_001136016 4071 APP NP_001129603 4333 NM_001136129 4072 ASPA NP_000040 4334 NM_001128085 4073 ASPA NP_001121557 4335 NM_000049 4074 S1PR1 NP_001391 4336 NM_001400 4075 IDS NP_001160022 4337 NM_001166550 4076 IDS NP_006114 4338 NM_006123 4077 IDS NP_000193 4339 NM_000202 4078 HTRA2 NP_659540 4340 NM_013247 4079 HTRA2 NP_037379 4341 NM_145074 4080 CDNF NP_001025125 4342 NM_001029954 4081 DNAJC5 NP_079495 4343 NM_025219 4082 IDUA NP_000194 4344 NM_000203 4083 SPON1 NP_006099 4345 NM_006108 4084 NMNAT2 NP_733820 4346 NM_015039 4085 NMNAT2 NP_055854 4347 NM_170706 4086 FMR1 NP_002015 4348 NM_002024 4087 MECP2 NP_004983 4349 NM_001110792 4088 MECP2 NP_001104262 4350 NM_004992 4089 GNS NP_002067 4351 NM_002076 4090 VEGFB NP_003368 4352 NM_003377 4091 HIF1A NP_851397 4353 NM_181054 4092 HIF1A NP_001521 4354 NM_001530 4093 SERPINF1 NP_002606 4355 NM_002615 4094 VEGFA NP_001165093 4356 NM_001025369 4095 VEGFA NP_001165094 4357 NM_001025366 4096 VEGFA NP_001020540 4358 NM_001025367 4097 VEGFA NP_001020541 4359 NM_001025368 4098 VEGFA NP_003367 4360 NM_003376 4099 VEGFA NP_001165101 4361 NM_001171627 4100 VEGFA NP_001020537 4362 NM_001171626 4101 VEGFA NP_001165100 4363 NM_001171629 4102 VEGFA NP_001020539 4364 NM_001171628 4103 VEGFA NP_001020538 4365 NM_001171624 4104 VEGFA NP_001028928 4366 NM_001171630 4105 VEGFA NP_001165098 4367 NM_001171625 4106 VEGFA NP_001165097 4368 NM_001171622 4107 VEGFA NP_001165096 4369 NM_001171623 4108 VEGFA NP_001165095 4370 NM_001033756 4109 VEGFA NP_001165099 4371 NM_001025370 4110 STC1 NP_003146 4372 NM_003155 4111 NGB NP_067080 4373 NM_021257 4112 NFE2L2 NP_001138884 4374 NM_006164 4113 NFE2L2 NP_006155 4375 NM_001145412 4114 NFE2L2 NP_001138885 4376 NM_001145413 4115 MAPK7 NP_620603 4377 NM_002749 4116 MAPK7 NP_620602 4378 NM_139034 4117 MAPK7 NP_620601 4379 NM_139033 4118 MAPK7 NP_002740 4380 NM_139032 4119 NMNAT1 NP_073624 4381 NM_022787 4120 NGF NP_002497 4382 NM_002506 4121 NAGLU NP_000254 4383 NM_000263 4122 CLU NP_001822 4384 NM_001831 4123 MME NP_009218 4385 NM_000902 4124 MME NP_009219 4386 NM_007289 4125 MME NP_000893 4387 NM_007287 4126 MME NP_009220 4388 NM_007288 4127 CTSA NP_001121167 4389 NM_001167594 4128 CTSA NP_000299 4390 NM_000308 4129 CTSA NP_001161066 4391 NM_001127695 4130 PPT1 NP_000301 4392 NM_000310 4131 PPT1 NP_001136076 4393 NM_001142604 4132 TIMP2 NP_003246 4394 NM_003255 4133 MANF NP_006001 4395 NM_006010 4134 TIMP1 NP_003245 4396 NM_003254 4135 GAD2 NP_000809 4397 NM_001134366 4136 GAD2 NP_001127838 4398 NM_000818 4137 GALC NP_000144 4399 NM_000153 4138 GAD1 NP_000808 4400 NM_013445 4139 GAD1 NP_038473 4401 NM_000817 4140 NTF3 NP_002518 4402 NM_002527 4141 NTF3 NP_001096124 4403 NM_001102654 4142 GUSB NP_000172 4404 NM_000181 4143 HGF NP_001010932 4405 NM_001010933 4144 HGF NP_001010931 4406 NM_001010932 4145 HGF NP_001010934 4407 NM_001010931 4146 HGF NP_000592 4408 NM_000601 4147 HGF NP_001010933 4409 NM_001010934 4148 SERPINI1 NP_005016 4410 NM_005025 4149 SERPINI1 NP_001116224 4411 NM_001122752 4150 RGS2 NP_002914 4412 NM_002923 4151 NPY NP_000896 4413 NM_000905 4152 UCP2 NP_003346 4414 NM_003355 4153 SST NP_001039 4415 NM_001048 4154 SGSH NP_000190 4416 NM_000199 4155 CYP2J2 NP_000766 4417 NM_000775 4156 GM2A NP_000396 4418 NM_000405 4157 GM2A NP_001161079 4419 NM_001167607 4158 HEXA NP_000511 4420 NM_000520 4159 UCHE1 NP_004172 4421 NM_004181 4160 HEXB NP_000512 4422 NM_000521 4161 PINK1 NP_115785 4423 NM_032409 4162 PRDX3 NP_006784 4424 NM_006793 4163 PRDX1 NP_859048 4425 NM_002574 4164 PRDX1 NP_859047 4426 NM_181696 4165 PRDX1 NP_002565 4427 NM_181697 4166 GEB1 NP_001129074 4428 NM_001135602 4167 GEB1 NP_001073279 4429 NM_000404 4168 GEB1 NP_000395 4430 NM_001079811 4169 TPP1 NP_000382 4431 NM_000391 4170 ANG NP_001136 4432 NM_001097577 4171 ANG NP_001091046 4433 NM_001145 4172 HMOX1 NP_002124 4434 NM_002133 4173 NRG1 NP_039258 4435 NM_001160001 4174 NRG1 NP_001153479 4436 NM_001159995 4175 NRG1 NP_001153476 4437 NM_001160007 4176 NRG1 NP_001153477 4438 NM_001160008 4177 NRG1 NP_039254 4439 NM_001159996 4178 NRG1 NP_039256 4440 NM_001159999 4179 NRG1 NP_001153467 4441 NM_001160002 4180 NRG1 NP_001153468 4442 NM_001160004 4181 NRG1 NP_039250 4443 NM_004495 4182 NRG1 NP_001153471 4444 NM_001160005 4183 NRG1 NP_001153480 4445 NM_013964 4184 NRG1 NP_039251 4446 NM_013960 4185 NRG1 NP_039252 4447 NM_013962 4186 NRG1 NP_039253 4448 NM_013959 4187 NRG1 NP_001153474 4449 NM_013958 4188 NRG1 NP_004486 4450 NM_013957 4189 NRG1 NP_001153473 4451 NM_013956 4190 NFIL3 NP_005375 4452 NM_005384 4191 MAN2B1 NP_000519 4453 NM_000528 4192 DHCR24 NP_055577 4454 NM_014762 4193 DDC NP_001076440 4455 NM_001082971 4194 DDC NP_000781 4456 NM_000790 4195 TP53 NP_001119588 4457 NM_001126113 4196 TP53 NP_001119589 4458 NM_001126112 4197 TP53 NP_001119585 4459 NM_000546 4198 TP53 NP_001119584 4460 NM_001126116 4199 TP53 NP_001119587 4461 NM_001126117 4200 TP53 NP_001119586 4462 NM_001126114 4201 TP53 NP_000537 4463 NM_001126115 4202 ADNP NP_056154 4464 NM_181442 4203 ADNP NP_852107 4465 NM_015339 4204 GAN NP_071324 4466 NM_022041 4205 GAL NP_057057 4467 NM_015973 4206 SMN1 NP_000335 4468 NM_022874 4207 SMN1 NP_075015 4469 NM_017411 4208 SMN1 NP_075014 4470 NM_000344 4209 SMN1 NP_059107 4471 NM_022876 4210 SMN1 NP_075013 4510 NM_022875 4211 SMN1 NP_075012 4511 NM_022877 4212 PROC NP_000303 4512 NM_000312 4213 TRAP1 NP_057376 4513 NM_016292 4214 I118BP NP_001138527 4514 NM_173042 4215 I118BP NP_001138529 4515 NM_001145057 4216 I118BP NP_766630 4516 NM_001145055 4217 I118BP NP_001034749 4517 NM_001039660 4218 I118BP NP_001034748 4518 NM_001039659 4219 PRDX6 NP_004896 4519 NM_004905 4220 TXN NP_003320 4520 NM_003329 4221 GAA NP_000143 4521 NM_000152 4222 GAA NP_001073271 4522 NM_001079803 4223 GAA NP_001073272 4523 NM_001079804 4224 GHRL NP_001128416 4524 NM_001134945 4225 GHRL NP_001128417 4525 NM_001134944 4226 GHRL NP_001128413 4526 NM_001134946 4227 GHRL NP_057446 4527 NM_016362 4228 GHRL NP_001128418 4528 NM_001134941 4229 CSF3 NP_757373 4529 NM_000759 4230 CSF3 NP_757374 4530 NM_172220 4231 CSF3 NP_000750 4531 NM_172219 4232 UBE3A NP_000453 4532 NM_130838 4233 UBE3A NP_570854 4533 NM_130839 4234 UBE3A NP_570853 4534 NM_000462 4235 ABCD1 NP_000024 4535 NM_000033 4236 NDP NP_000257 4536 NM_000266 4237 TH NP_954986 4537 NM_199292 4238 TH NP_954987 4538 NM_199293 4239 TH NP_000351 4539 NM_000360 4240 GCH1 NP_000152 4540 NM_000161 4241 GCH1 NP_001019241 4541 NM_001024070 4242 GCH1 NP_001019242 4542 NM_001024071 4243 GCH1 NP_001019195 4543 NM_001024024 4244 BCL2 NP_000648 4544 NM_000633 4245 BCL2 NP_000624 4545 NM_000657 4246 ENO2 NP_001966 4546 NM_001975 4247 EPO NP_000790 4547 NM_000799 4248 GBA NP_001005741 4548 NM_001005742 4249 GBA NP_001165283 4549 NM_001005741 4250 GBA NP_001005742 4550 NM_001171811 4251 GBA NP_001165282 4551 NM_001171812 4252 GBA NP_000148 4552 NM_000157 4253 AGA NP_000018 4553 NM_000027 4254 AGA NP_001165459 4554 NM_001171988 4255 UPF1 NP_002902 4555 NM_002911 4256 PSAP NP_001035931 4556 NM_001042465 4257 PSAP NP_002769 4557 NM_001042466 4258 PSAP NP_001035930 4558 NM_002778 4259 ANXA1 NP_000691 4559 NM_000700 4260 IGF1 NP_001104753 4560 NM_001111284 4261 IGF1 NP_001104754 4561 NM_001111283 4262 IGF1 NP_000609 4562 NM_000618 4263 IGF2 NP_001035835 4563 NM_001007139 4264 IGF2 NP_000603 4564 NM_000612 4265 IGF2 NP_001007140 4565 NM_000207 4266 IGF2 NP_001121070 4566 NM_001127598 4267 IGF2 NP_000198 4567 NM_001042376 4268 PARK2 NP_054642 4568 NM_013988 4269 PARK2 NP_054643 4569 NM_013987 4270 PARK2 NP_004553 4570 NM_004562 4271 FUCA1 NP_000138 4571 NM_000147 4272 SIRT1 NP_001135970 4572 NM_012238 4273 SIRT1 NP_036370 4573 NM_001142498 4274 PARK7 NP_001116849 4574 NM_007262 4275 PARK7 NP_009193 4575 NM_001123377 4276 ANXA2 NP_004030 4576 NM_004039 4277 ANXA2 NP_001002857 4577 NM_001136015 4278 ANXA2 NP_001002858 4578 NM_001002858 4279 ANXA2 NP_001129487 4579 NM_001002857 4280 GCG NP_002045 4580 NM_002054 4281 LEP NP_000221 4581 NM_000230 4282 SH3BP5 NP_004835 4582 NM_001018009 4283 SH3BP5 NP_001018009 4583 NM_004844 4284 CNTF NP_000605 4584 NM_053023 4285 CNTF NP_444251 4585 NM_000614 4286 GLA NP_000160 4586 NM_000169 4287 KCNN3 NP_740752 4587 NM_170782 4288 KCNN3 NP_002240 4588 NM_002249 4289 ARSA NP_001078896 4589 NM_000487 4290 ARSA NP_001078897 4590 NM_001085428 4291 ARSA NP_000478 4591 NM_001085426 4292 ARSA NP_001078894 4592 NM_001085427 4293 ARSA NP_001078895 4593 NM_001085425 4294 SUMF1 NP_001158147 4594 NM_001164674 4295 SUMF1 NP_001158146 4595 NM_001164675 4296 SUMF1 NP_877437 4596 NM_182760 4297 CRH NP_000747 4597 NM_000756 4298 SMPD1 NP_000534 4598 NM_000543 4299 SMPD1 NP_001007594 4599 NM_001007593 4300 Table 4.

It should be noted that any of the sequences described herein (e.g., the Toxoplasma secreted protein and/or the therapeutic polypeptides) can be codon optimized for expression in a target cell (e.g., Toxoplasma). Examples of such sequence modifications include, but are not limited to, an altered G/C content to more closely approach that typically found in the target cell species of interest, and the removal of codons atypically found in the target cell a species commonly referred to as codon optimization.

The phrase “codon optimization” refers to the selection of appropriate DNA nucleotides for use within a structural gene or fragment thereof that approaches codon usage within the target cell of interest. Therefore, an optimized gene or nucleic acid sequence refers to a gene in which the nucleotide sequence of a native or naturally occurring gene has been modified in order to utilize statistically-preferred or statistically-favored codons within the target cell. The nucleotide sequence typically is examined at the DNA level and the coding region optimized for expression in the target cell species determined using any suitable procedure. In this method, the standard deviation of codon usage, a measure of codon usage bias, may be calculated by first finding the squared proportional deviation of usage of each codon of the native gene relative to that of highly expressed target cell genes, followed by a calculation of the average squared deviation. The formula used is: 1 SDCU=n=1N[(Xn−Yn)/Yn]2/N, where Xn refers to the frequency of usage of codon n in highly expressed target cell genes, where Yn to the frequency of usage of codon n in the gene of interest and N refers to the total number of codons in the gene of interest.

One method of optimizing the nucleic acid sequence in accordance with the preferred codon usage for a particular target cell type is based on the direct use, without performing any extra statistical calculations, of codon optimization Tables such as those provided on-line at the Codon Usage Database through the Codon usage tabulated from international DNA sequence databases: status for the year 2000. Y Nakamura, T Gojobori, T Ikemura—Nucleic acids research, 2000—Oxford Univ Press. The Codon Usage Database contains codon usage tables for a number of different species, with each codon usage Table having been statistically determined based on the data present in Genbank.

By using the above Tables to determine the most preferred or most favored codons for each amino acid in a particular species (for example, Toxoplasma gondii), a naturally-occurring nucleotide sequence encoding a protein of interest can be codon optimized for that particular target cell species. This is effected by replacing codons that may have a low statistical incidence in the particular species genome with corresponding codons, in regard to an amino acid, that are statistically more favored. However, one or more less-favored codons may be selected to delete existing restriction sites, to create new ones at potentially useful junctions (5′ and 3′ ends to add signal peptide or termination cassettes, internal sites that might be used to cut and splice segments together to produce a correct full-length sequence), or to eliminate nucleotide sequences that may negatively effect mRNA stability or expression.

The naturally-occurring encoding nucleotide sequence may already, in advance of any modification, contain a number of codons that correspond to a statistically-favored codon in a particular target cell species. Therefore, codon optimization of the native nucleotide sequence may comprise determining which codons, within the native nucleotide sequence, are not statistically-favored with regards to a particular target cell, and modifying these codons in accordance with a codon usage table of the particular target cell to produce a codon optimized derivative. A modified nucleotide sequence may be fully or partially optimized for target cell codon usage provided that the protein encoded by the modified nucleotide sequence is produced at a level higher than the protein encoded by the corresponding naturally occurring or native gene. Additionally or alternatively, codon optimized/usage sequence can fold better than the protein encoded by the corresponding naturally occurring or native gene. Additionally or alternatively, codon optimized/usage sequence is targeted better to the target organelle(s) than the protein encoded by the corresponding naturally occurring or native gene. Additionally or alternatively, codon optimized/usage sequence is less degraded than the protein encoded by the corresponding naturally occurring or native gene.

For example, the following Table 5 of Toxoplasma codon usage can be used.

TABLE 5 Amino acid Frequency: per Triplet (one letter code) Fraction thousand UUU F 0.35 13.3 UUC F 0.65 25 UUA L 0.03 2.6 UUG L 0.17 14.5 CUU L 0.17 15 CUC L 0.31 27.1 CUA L 0.04 3.8 CUG L 0.28 24 AUU I 0.38 12.2 AUC I 0.53 17.4 AUA I 0.09 2.9 AUG M 1 18.3 GUU V 0.22 14.7 GUC V 0.38 25.4 GUA V 0.08 5.7 GUG V 0.32 21.4 UCU S 0.23 20.3 UCC S 0.17 15.2 UCA S 0.09 8.1 UCG S 0.22 19 CCU P 0.27 15.4 CCC P 0.24 13.6 CCA P 0.18 10.4 CCG P 0.3 17.3 ACU T 0.22 12.3 ACC T 0.24 13 ACA T 0.24 13.2 ACG T 0.3 16.4 GCU A 0.21 20.5 GCC A 0.24 22.6 GCA A 0.22 20.8 GCG A 0.33 31.5 UAU Y 0.26 5.1 UAC Y 0.74 14.5 UAA * 0.34 0.6 UAG * 0.23 0.4 CAU H 0.37 7.9 CAC H 0.63 13.4 CAA Q 0.36 13.7 CAG Q 0.64 24.5 AAU N 0.35 10.1 AAC N 0.65 18.9 AAA K 0.38 18.4 AAG K 0.62 29.8 GAU D 0.32 16.3 GAC D 0.68 34.3 GAA E 0.45 32.7 GAG E 0.55 40.6 UGU C 0.37 7.2 UGC C 0.63 12.4 UGA * 0.43 0.8 UGG W 1 10.8 CGU R 0.12 8.2 CGC R 0.25 17.5 CGA R 0.18 12.7 CGG R 0.14 10.1 AGU S 0.11 9.3 AGC S 0.18 16.1 AGA R 0.18 12.8 AGG R 0.12 8.7 GGU G 0.18 14.6 GGC G 0.36 28.5 GGA G 0.27 21.4 GGG G 0.18 14.6 Table 5.

According to some embodiments of the invention, the heterologous polynucleotide further comprises a nucleic acid sequence encoding a selectable marker.

According to some embodiments of the invention, the selectable marker comprises chloramphenicol acetyltransferase (CAT), DHFR-TS, BLE, HXGPRT, UPRT, TK, CD, a fluorescent protein (such as GFP, YFP, RFP, mCherry or other) or an epitope tag (such as HA, Myc, Ty-1, FLAG or other).

According to some embodiments of the invention, the selectable marker comprises HXGPRT.

Toxoplasma tachyzoites deficient in HXGPRT activity can be selected in the presence of 6-thioxanthine (6-TX), whereas strains expressing HXGPRT activity can be selected in mycophenolic acid (MPA) and/or xanthine (Pfefferkorn and Borotz, 1994, Pfefferkorn E. R., Borotz S. (1994) Exp. Parasitol. 79, 374-382).

According to some embodiments of the invention, the selectable marker comprises chloramphenicol acetyltransferase (CAT) (for positive selection using Chloramphenicol), DHFR-TS (for positive selection using Pyrimethamine), BLE (for positive selection using Phleomycin), HXGPRT (for positive selection using Mycophenolic acid+xanthine or negative selection using 6-thioxanthine, UPRT (for negative selection using 5′-fluo-2′-deoxyuridine), TK (for positive selection using Ganciclovir), CD (for positive selection using 5-fluorocytosine), a fluorescent protein (such as GFP, YFP, RFP, mCherry or other) or an epitope tag (such as HA, Myc, Ty-1, FLAG or other).

According to some embodiments of the invention, the nucleic acid construct further comprises a third nucleic acid sequence encoding an inducible self-destruction element.

According to some embodiments of the invention, the inducible self destruction element is in the same frame as the therapeutic cassette.

According to some embodiments of the invention, the inducible self destruction element is in a separate reading frame, regulated by different regulatory elements. For instance, the therapeutic cassette can be driven by a latent-stage promoter, while the self-destruction cassette will be driven by a drug-inducible promoter.

According to some embodiments of the invention, the inducible self-destruction element is active in response to a drug.

According to some embodiments of the invention, the drug comprises an antibiotic.

According to some embodiments of the invention, the third nucleic acid sequence encoding the inducible self-destruction element is comprised in the same nucleic acid construct which comprises the heterologous polynucleotide comprising the first nucleic acid sequence encoding the Toxoplasma secreted protein in frame fused upstream to the second nucleic acid sequence encoding the pharmaceutical polypeptide.

According to some embodiments of the invention, the third nucleic acid sequence encoding the inducible self-destruction element is comprised in a separate nucleic acid construct with respect to the nucleic acid construct which comprises the heterologous polynucleotide comprising the first nucleic acid sequence encoding the Toxoplasma secreted protein in frame fused upstream to the second nucleic acid sequence encoding the pharmaceutical polypeptide.

According to some embodiments of the invention, the Toxoplasma untranslated region (UTR) nucleic acid sequence is upstream and/or downstream of the open reading frame of the selectable marker and/or of the self-destruction element.

According to an aspect of some embodiments of the present invention there is provided a nucleic acid construct system comprising at least two nucleic acid constructs, wherein a first nucleic acid construct of the at least two nucleic acid constructs is the nucleic acid construct of some embodiments of the invention, and a second nucleic construct of the at least two nucleic acid constructs comprises a polynucleotide encoding a selectable marker.

Typical cloning vectors may also contain a transcription and translation initiation sequence, transcription and translation terminator and a polyadenylation signal.

Following is a non-limiting list of Toxoplasma nucleic acid constructs which can be used as a backbone to generate the nucleic acid construct of some embodiments of the invention: pGRA, pUPRT, pROP1, pTUB1, pTUB8, pLIC, pTOXO, pMIC2, pHX, pCAT, pDHFR, pBlueScript, pTetO7SAG1, pTetO7SAG4, pSAG1, pSAG4, pHTU, pTKO, pLoxP-DHFR, pminCAT/HXGPRT+, pminCAT/HXGPRT−, pDHFR-TSc3/M3, pDHFR-TSc3/M2M3, pminiHXGPRT, and pUC19. These vectors can be obtained from various sources, such as the nonprofit plasmid repository “addgene”; the NIH AIDS Reagent Program; Agilent Technologies; NEB; Thermo Fisher Scientific; Sigma Aldrich; GenScript; and MoBiTec GmbH.

Table 6 hereinbelow provides non-limiting exemplary vectors and catalogue numbers.

TABLE 6 Vector Backbones Catalogue Construct name Manufacturer number pLIC Addgene 27989 pCAT Addgene 59018 pTetO7SAG1 Addgene 59017 pSAG1 Addgene 54467 pUPRT Addgene 58528 pLoxP-DHFR Addgene 70147 pminCAT/HXGPRT+ NIH AIDS Reagent Program 2850 pminCAT/HXGPRT− NIH AIDS Reagent Program 2851 pDHFR-TSc3/M3 NIH AIDS Reagent Program 2853 pDHFR-TSc3/M2M3 NIH AIDS Reagent Program 2854 pminiHXGPRT NIH AIDS Reagent Program 2855 pBlueScript Agilent Technologies 200252, 200251, 212205, 212206, 212207, 212208, 212240, 212250 pUC19 Addgene; 50005; NEB; N3041; Thermo Fisher Scientific; SD0061; Sigma Aldrich; D3404; MoBiTec GmbH V33202 Table 6.

According to an aspect of some embodiments of the present invention there is provided a Toxoplasma transformed with the nucleic acid construct of some embodiments of the invention or with the nucleic acid construct system of some embodiments of the invention.

As used herein the term “Toxoplasma” refers to the intracellular, parasitic protozoan Toxoplasma gondii.

Non-limiting examples of a Toxoplasma gondii strains which can be used along with the construct and methods of some embodiments of the invention include:

(i) Type I—including but not limited to: GT1, RH, ENT, VEL, TgCatCo1 and CAST.

(ii) Type II—including but not limited to: ME49, Beverly, PDS, PLK, PTG, DEG, PIH, TgNmBr1 and PRU.

(iii) Type III—including but not limited to: VEG, C56, CTG, CEP, TgGoatUS4 and STRL.

(iv) Type Atypical—including but not limited to: TgCTPrC3, TgBbUS1, TgRabbitBr1 and TgPigUS15.

According to some embodiments of the invention, the Toxoplasma is not attenuated.

As is conventional in the art, the term “attenuated” refers to a weakened and/or less vigorous strain of T. gondii as compared to a native (wild type) T. gondii which is non-genetically modified. Usually, an attenuated mutant of T. gondii is capable of stimulating an immune response and creating immunity but not causing illness. Attenuation can be achieved by conventional methods including, but not limited, to γ-irradiation or the generation of a pyrimidine auxotroph.

Non-limiting examples of attenuated Toxoplasma are described in US 20120045477 Al and U.S. Pat. No. 8,673,289 B2, which are fully incorporated herein by reference.

It should be noted that T. gondii replication is essential for its ability to disseminate in the body and reach distal tissues during the acute stage of infection, its ability to persist in the infected cells and its ability to establish chronic cysts in the host.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention is characterized by a higher proliferation rate as compared to the proliferation rate of an attenuated Toxoplasma.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention is not an auxotroph.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention comprises a functional endogenous pathway suitable for de-novo biosynthesis of pyrimidines.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention is capable of differentiation into the Bradizoite stage.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention is capable of RNA synthesis and/or DNA replication.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention is capable of RNA synthesis.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention is capable of DNA replication.

According to some embodiments of the invention, the Toxoplasma of some embodiments of the invention comprises an endogenous functional Carbamoyl phosphate synthetase II (CPSII) enzyme (as described in U.S. Pat. No. 8,673,289), e.g., as provided in any of SEQ ID NOs: 4612-4617.

The constructs and Toxoplasma of some embodiments of the invention can be used to deliver a protein-of-interest into the subject, e.g., into a specific tissue or cell type of the subject.

According to an aspect of some embodiments of the present invention there is provided a method of administering a protein-of-interest into a tissue-of-interest of a subject, the method comprising administering to the subject the Toxoplasma of some embodiments of the invention or the pharmaceutical composition of some embodiments of the invention, thereby administering the protein-of-interest to the tissue-of-interest of the subject.

Examples of tissue-of-interest include, but are not limited to, a central nervous system, muscles, parts of the eye, blood, lymph nodes, spleen, white blood cells, digestive system, and lamina propria.

It should be noted that since the Toxoplasma can cross the blood brain barrier it can deliver the protein-of-interest into the central nervous system of the subject in need thereof.

According to an aspect of some embodiments of the present invention there is provided a method of administering a protein-of-interest into a central nervous system of a subject, the method comprising administering to the subject the Toxoplasma of some embodiments of the invention or the pharmaceutical composition of some embodiments of the invention, thereby administering the protein-of-interest to the central nervous system of the subject.

Thus, the Toxoplasma of some embodiments of the invention can be used to treat a subject in need thereof by delivering a protein-of-interest (e.g., a therapeutic polypeptide) which is capable of treating the subject.

According to an aspect of some embodiments of the present invention there is provided a method of treating a subject in need thereof, comprising administering to the subject the Toxoplasma of some embodiments of the invention or the pharmaceutical composition of some embodiments of the invention, wherein the subject is diagnosed with a pathology treatable by administration of the pharmaceutical polypeptide in a central nervous system of the subject, thereby treating the subject in need thereof.

According to an aspect of some embodiments of the present invention there is provided a method of treating a subject in need thereof, comprising administering to the subject a Toxoplasma comprising a nucleic acid construct which comprises a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein the heterologous polynucleotide is operably linked to a promoter for directing transcription of the heterologous polynucleotide in a Toxoplasma, wherein the subject is diagnosed with a pathology treatable by administration of the pharmaceutical polypeptide in a central nervous system of the subject, thereby treating the subject in need thereof.

The term “treating” refers to inhibiting, preventing or arresting the development of a pathology (disease, disorder or condition) and/or causing the reduction, remission, or regression of a pathology. Those of skill in the art will understand that various methodologies and assays can be used to assess the development of a pathology, and similarly, various methodologies and assays may be used to assess the reduction, remission or regression of a pathology.

As used herein, the term “preventing” refers to keeping a disease, disorder or condition from occurring in a subject who may be at risk for the disease, but has not yet been diagnosed as having the disease.

As used herein, the term “subject” includes mammals, preferably human beings at any age which suffer from the pathology. Preferably, this term encompasses individuals who are at risk to develop the pathology.

According to some embodiments of the invention, the subject is diagnosed with a pathology characterized by a deficient endogenous protein in a central nervous system of a subject.

According to some embodiments of the invention, the deficient endogenous protein comprises a deletion, insertion, and/or substitution of at least one amino acid of the endogenous protein as compared to a wild type amino acid sequence of the endogenous protein.

According to some embodiments of the invention, the deficient endogenous protein comprises a reduced level of the endogenous protein as compared to a level of the endogenous protein in a healthy subject devoid of the pathology.

According to some embodiments of the invention, the deficient endogenous protein is absence of the endogenous protein in the subject diagnosed with the pathology.

According to some embodiments of the invention, the subject is diagnosed with Krabbe disease.

According to some embodiments of the invention, the subject is diagnosed with Rett syndrome.

According to some embodiments of the invention, the subject is diagnosed with Canavan disease.

According to some embodiments of the invention, the subject is diagnosed with Spinal Muscular Atrophy.

According to some embodiments of the invention, the subject is diagnosed with Parkinson's disease.

According to some embodiments of the invention, the subject is diagnosed with hypoxic/ischemic or neuroinflammatory CNS disorder.

According to some embodiments of the invention, the subject is diagnosed with Alzheimer's disease.

According to some embodiments of the invention, the subject is diagnosed with Amyotrophic Lateral Sclerosis.

According to some embodiments of the invention, the subject is diagnosed with Huntington's disease.

According to some embodiments of the invention, the subject is diagnosed with a lysosomal storage disease.

According to some embodiments of the invention, the subject is diagnosed with MECP2-duplication syndrome.

According to some embodiments of the invention the subject does not a have a compromised immune system. Examples of subjects with compromised immune system include, but are not limited to AIDS patients, subjects receiving chemotherapy, subjects receiving immunosuppressant drugs such as for cell, tissue and/or organ transplantation.

According to some embodiments of the invention, the method further comprising administering to the subject a drug capable of inducing the self-destruction element.

According to some embodiments of the invention, the method further comprising administering to the subject a molecule necessary for sustaining the Toxoplasma inside the host cell and/or body.

According to some embodiments of the invention, the molecule necessary for sustaining the Toxoplasma is an antibiotic.

According to some embodiments of the invention, the molecule necessary for sustaining the Toxoplasma is a small-molecule.

According to some embodiments of the invention, the molecule necessary for sustaining the Toxoplasma is a metabolite.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug prior to administration of the Toxoplasma and/or subsequent to administration of the Toxoplasma and/or concomitantly with administration of the Toxoplasma to the subject.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug prior to administration of the Toxoplasma to the subject.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug subsequent (or following) to administration of the Toxoplasma to the subject.

According to some embodiments of the invention, the method further comprises administering to the subject an immunosuppression drug concomitantly with administration of the Toxoplasma to the subject.

According to some embodiments of the invention, administering is performed by peripheral administration.

According to some embodiments of the invention, the peripheral administration comprises intravenous administration.

According to some embodiments of the invention, the peripheral administration comprises oral administration.

According to some embodiments of the invention, administering is performed by intraperitoneal injection.

According to some embodiments of the invention, administering is performed by intramuscular injection.

According to some embodiments of the invention, administering is performed by aerosols.

According to some embodiments of the invention, administering is performed by direct administration to the central nervous system or an adjacent tissue thereof.

According to some embodiments of the invention, the disease which is treated by the methods of some embodiments of the invention, e.g., using the Toxoplasma and/or the pharmaceutical composition comprising same is any of the diseases listed in Table 7 hereinabove.

Table 7 lists non-limiting diseases associated with deficient or abnormal expression or function of the endogenous proteins, which can be treated by administration of the therapeutic polypeptide of some embodiments of the invention.

TABLE 7 Gene Name/Symbol Associated disease TFEB Lysosomal storage diseases and neurodegenerative diseases HGSNAT Mucopolysaccharidosis 3C (Sanfilippo syndrome C) MEF2C Parkinson's disease NRTN Parkinson's disease PGF Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. RPE65 Leber congenital amaurosis, retinitis pigmentosa GDNF Parkinson's disease, Supranuclear Palsy, Multiple sclerosis, Alzheimers disease, Amyotrophic Lateral Sclerosis, Huntington's disease, retinal degenerations, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. CNGB3 Achromatopsia BDNF Amyotrophic Lateral Sclerosis, Huntington's disease, Alzheimer's disease, Spinal Cord Injury, Obesity, Lysosomal storage disorders. APP Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. ASPA Canavan disease S1PR1 Multiple sclerosis IDS Mucopolysaccharidosis type II (Hunter Syndrome, iduronate sulfatase deficiency) HTRA2 Parkinson's disease, Alzheimer's disease CDNF Parkinson's Disease, Alzheimers Disease, Amyotrophic Lateral Sclerosis DNAJC5 neurodegenerative disorders IDUA Mucopolysaccharidosis type I (Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome) SPON1 Alzheimer's disease NMNAT2 disorders involving axonal degenerations, such as Taxol-induced neuropathy, multiple sclerosis, some viral disorders, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. FMR1 Fragile X syndrome MECP2 Rett syndrome GNS Mucopolysaccharidosis 3D (Sanfilippo syndrome D) VEGFB Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. HIF1A Alzheimer's disease SERPINF1 Parkinson's Disease, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. VEGFA Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. STC1 retinal degeneration, optic nerve diseases, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. NGB optic atrophy, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. NFE2L2 MAPK7 Alzheimer's disease NMNAT1 Parkinsons disease, Leber Congential Amaurosis, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. NGF Amyotrophic Lateral Sclerosis, Alzheimer's disease, down syndrome, sensory neuropathies NAGLU Mucopolysaccharidosis 3B (Sanfilippo syndrome B) CLU Alzheimer's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. MME Alzheimer's disease CTSA Galactosialidosis PPT1 ceroid lipofuscinosis neuronal type 1 (Batten disease) TIMP2 Multiple sclerosis, Alzheimer's disease, and Huntington's disease, Parkinson's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. MANF Parkinson's disease, retinitis pigmentosa, retinal artery occlusion, diabetes, Wolfram's syndrome, Alzheimer's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. TIMP1 Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GAD2 Parkinson's disease GALC Krabbe disease (globoid cell leukodystrophy) GAD1 Parkinson's disease NTF3 Charcot-Marie-Tooth disease, multiple sclerosis, Spinal Cord Injury, X-linked adrenoleukodystrophy, diabetic neuropathies, axonal neuropathies, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GUSB Sly syndrome HGF amyotrophic lateral sclerosis SERPINI1 Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. RGS2 anxiety disorders NPY epilepsy, Post-Traumatic Stress Disorder UCP2 acute and excitotoxic brain injury, Parkinsons disease, SST epilepsy, alzheimer's disease, SGSH Mucopolysaccharidosis 3A (Sanfilippo syndrome A) CYP2J2 Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GM2A GM2 gangliosidoses (Tay-Sachs disease (TSD), Sandhoff- Jatzkewitz disease, GM2 activator deficiency) HEXA GM2 gangliosidoses (Tay-Sachs disease (TSD), Sandhoff- Jatzkewitz disease, GM2 activator deficiency) UCH11 Alzheimer's disease HEXB GM2 gangliosidoses (Tay-Sachs disease (TSD), Sandhoff- Jatzkewitz disease, GM2 activator deficiency) PINK1 Parkinson's disease PRDX3 Amyotrophic Lateral Sclerosis, parkinsons disease, alzheimers disease PRDX1 Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GLB1 GM1 gangliosidosis TPP1 ceroid lipofuscinosis neuronal type 2 (Batten disease) ANG Amyotrophic Lateral Sclerosis, Parkinson's disease HMOX1 Alzheimer's (AD), Parkinson's (PD), Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. NRG1 Charcot-Marie-Tooth disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. NFIL3 Amyotrophic Lateral Sclerosis MAN2B1 alpha-Mannosidosis DHCR24 Alzheimer's disease. DDC Parkinson's disease, Aromatic L-amino-acid decarboxylase deficiency TP53 Brain tumors (Astrocytic tumours, Oligodendroglial tumours, Oligoastrocytic tumours, Ependymal tumours, Choroid plexus tumours, Other neuroepithelial tumours (Astroblastoma, Chordoid glioma of the third ventricle, Angiocentric glioma), Neuronal and mixed neuronal-glial tumours, Tumours of the pineal region, Embryonal tumours, Tumours of cranial and paraspinal nerves (Schwannoma, Neurofibroma, Perineurioma, Malignant peripheral nerve sheath tumour), Tumours of meningothelial cells, Mesenchymal tumours, Primary melanocytic lesions, Other neoplasms related to the meninges (Haemangioblastoma), Tumors of the haematopoietic system (Malignant Lymphomas, Plasmocytoma, Granulocytic sarcoma), Germ cell tumours (Germinoma, Embryonal carcinoma, Yolk sac tumour, Choriocarcinoma, Teratoma, Mixed germ cell tumours), Tumours of the sellar region (craniopharyngioma, Granular cell tumour, Pituicytoma, Spindle cell oncocytoma of the adenohypophysis), Metastatic Tumours). ADNP Alzheimer's disease, Amyotrophic Lateral Sclerosis, frontotemportal degeneration/dementia (FTD), Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GAN Giant Axonal Neuropathy GAL epilepsy, Alzheimer's disease, opiate addiction/withdrawel SMN1 Spinal muscular atrophy PROC Amyotrophic Lateral Sclerosis, Alzheimer's disease, multiple sclerosis, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. TRAP1 Parkinson's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. I118BP Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. PRDX6 Alzheimer's disease, Parkinson's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. TXN Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GAA Pompe disease GHRL Alzheimer's disease, Parkinson's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. CSF3 Parkinson's Disease, Amyotrophic Lateral Sclerosis, Cerebral Palsy, Alzheimer's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. UBE3A Angelman syndrome ABCD1 Adrenoleukodystrophy NDP Norrie disease, familial exudative vitreoretinopathy (FEVR), inner ear diseases TH Parkinson's disease GCH1 Parkinson's disease BCL2 Amyotrophic lateral sclerosis, Parkinson's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. ENO2 Alzheimers disease EPO Parkinson's disease, multiple sclerosis, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GBA Gaucher disease AGA Aspartylglucosaminuria UPF1 Amyotrophic Lateral Sclerosis PSAP Parkinson's disease, demyelination disorders, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. ANXA1 Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. IGF1 Amyotrophic Lateral Sclerosis, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. IGF2 Alzheimer's disease PARK2 Parkinson's disease, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. FUCA1 Fucosidosis SIRT1 Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer disease, Frontotemporal dementia, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. PARK7 Amyotrophic Lateral Sclerosis, Parkinsons disease ANXA2 Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GCG Brain insulin resistance in Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis LEP Alzheimer's disease, Obesity, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. SH3BP5 Alzheimer's disease. CNTF Parkinson's disease, Supranuclear Palsy, Multiple sclerosis, Alzheimers disease, Amyotrophic Fateral Sclerosis, Huntington's disease, retinal degenerations, Traumatic Brain Injury, hypoxic/ischaemic CNS disorders, neuroinflammatory diseases, including stroke and neurodegenerative conditions. GLA Fabry disease KCNN3 Alzheimer's disease ARSA Metachromatic leukodystrophy, Multiple sulfatase deficiency SUMF1 Multiple sulfatase deficiency, Mucopolysaccharidosis Type III A (Sanfilippo Disease Type A) CRH cerebral oedema SMPD1 Niemann-Pick disease Table 7.

According to some embodiments of the invention, the disease (pathology) is not cancer.

The nucleic acid construct, the nucleic acid construct system or the Toxoplasma transformed with the nucleic acid construct or with the nucleic acid construct system of some embodiments of the invention can be administered to an organism per se, or in a pharmaceutical composition where it is mixed with suitable carriers or excipients.

According to an aspect of some embodiments of the present invention there is provided a pharmaceutical composition comprising the Toxoplasma of some embodiments of the invention, and a pharmaceutically acceptable carrier.

According to some embodiments of the invention, the pharmaceutical composition is for treating a subject diagnosed with any of the pathologies described herein.

According to some embodiments of the invention, the pharmaceutical composition is for treating a subject diagnosed with a pathology characterized by a deficient endogenous protein in a central nervous system of a subject.

According to some embodiments of the invention, the pharmaceutical composition is for treating a subject diagnosed with a pathology which is treatable by administration of the pharmaceutical polypeptide in a central nervous system of a subject.

According to some embodiments of the invention, the pharmaceutical composition further comprises an immunosuppression agent.

As used herein a “pharmaceutical composition” refers to a preparation of one or more of the active ingredients described herein with other chemical components such as physiologically suitable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration of a compound to an organism.

Herein the term “active ingredient” refers to the nucleic acid construct, the nucleic acid construct system or the toxoplasma transformed with the nucleic acid construct or with the nucleic acid construct system of some embodiments of the invention accountable for the biological effect.

Hereinafter, the phrases “physiologically acceptable carrier” and “pharmaceutically acceptable carrier” which may be interchangeably used refer to a carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound. An adjuvant is included under these phrases.

Herein the term “excipient” refers to an inert substance added to a pharmaceutical composition to further facilitate administration of an active ingredient. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols.

Techniques for formulation and administration of drugs may be found in “Remington's Pharmaceutical Sciences,” Mack Publishing Co., Easton, Pa., latest edition, which is incorporated herein by reference.

Suitable routes of administration may, for example, include oral, rectal, transmucosal, especially transnasal, intestinal or parenteral delivery, including intramuscular, subcutaneous and intramedullary injections as well as intrathecal, direct intraventricular, intracardiac, e.g., into the right or left ventricular cavity, into the common coronary artery, intravenous, intraperitoneal, intranasal, or intraocular injections.

Conventional approaches for drug delivery to the central nervous system (CNS) include: neurosurgical strategies (e.g., intracerebral injection or intracerebroventricular infusion); molecular manipulation of the agent (e.g., production of a chimeric fusion protein that comprises a transport peptide that has an affinity for an endothelial cell surface molecule in combination with an agent that is itself incapable of crossing the BBB) in an attempt to exploit one of the endogenous transport pathways of the BBB; pharmacological strategies designed to increase the lipid solubility of an agent (e.g., conjugation of water-soluble agents to lipid or cholesterol carriers); and the transitory disruption of the integrity of the BBB by hyperosmotic disruption (resulting from the infusion of a mannitol solution into the carotid artery or the use of a biologically active agent such as an angiotensin peptide).

Alternately, one may administer the pharmaceutical composition in a local rather than systemic manner, for example, via injection of the pharmaceutical composition directly into a tissue region of a patient.

The term “tissue” refers to part of an organism consisting of cells designed to perform a function or functions. Examples include, but are not limited to, brain tissue, retina, skin tissue, hepatic tissue, pancreatic tissue, bone, cartilage, connective tissue, blood tissue, muscle tissue, cardiac tissue, vascular tissue, renal tissue, pulmonary tissue, gonadal tissue, hematopoietic tissue.

Pharmaceutical compositions of some embodiments of the invention may be manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, culturing, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. For example, manufacturing of toxoplasma can be by culturing the toxoplasma in cell cultures.

Pharmaceutical compositions for use in accordance with some embodiments of the invention thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients into preparations which, can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen.

For injection, the active ingredients of the pharmaceutical composition may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological salt buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

For oral administration, the pharmaceutical composition can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the pharmaceutical composition to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, foodstuff, slurries, suspensions, and the like, for oral ingestion by a patient. Pharmacological preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carbomethylcellulose; and/or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

Pharmaceutical compositions which can be used orally, include push-fit capsules made of gelatin as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules may contain the active ingredients in admixture with filler such as lactose, binders such as starches, lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active ingredients may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for the chosen route of administration.

For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.

For administration by nasal inhalation, the active ingredients for use according to some embodiments of the invention are conveniently delivered in the form of an aerosol spray presentation from a pressurized pack or a nebulizer with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichloro-tetrafluoroethane or carbon dioxide. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in a dispenser may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

The pharmaceutical composition described herein may be formulated for parenteral administration, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multidose containers with optionally, an added preservative. The compositions may be suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.

Pharmaceutical compositions for parenteral administration include aqueous solutions of the active preparation in water-soluble form. Additionally, suspensions of the active ingredients may be prepared as appropriate oily or water based injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acids esters such as ethyl oleate, triglycerides or liposomes. Aqueous injection suspensions may contain substances, which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the active ingredients to allow for the preparation of highly concentrated solutions.

Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water based solution, before use.

The pharmaceutical composition of some embodiments of the invention may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides.

Pharmaceutical compositions suitable for use in context of some embodiments of the invention include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of active ingredients (e.g., the nucleic acid construct, the nucleic acid construct system or the toxoplasma transformed with the nucleic acid construct or with the nucleic acid construct system of some embodiments of the invention) effective to prevent, alleviate or ameliorate symptoms of a disorder (e.g., a disorder affecting the central nervous system of the subject) or prolong the survival of the subject being treated.

Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.

For any preparation used in the methods of the invention, the therapeutically effective amount or dose can be estimated initially from in-vitro assays, ex-vivo assays, cell culture assays, and/or animal models. For example, a dose can be formulated in animal models to achieve a desired concentration or titer. Such information can be used to more accurately determine useful doses in humans.

Toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. (See e.g., Fingl, et al., 1975, in “The Pharmacological Basis of Therapeutics”, Ch. 1 p. 1).

Dosage amount and interval may be adjusted individually to provide tissue levels (e.g., brain levels) of the active ingredient which are sufficient to induce or suppress the biological effect (minimal effective concentration, MEC). The MEC may vary for each preparation, but can be estimated from in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. Detection assays can be used to determine plasma, tissue or CSF (cerebro-spinal fluid) concentrations.

Depending on the severity and responsiveness of the condition to be treated, dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks, or e.g., a lifetime in the case of chronic diseases, or until cure is effected or diminution of the disease state is achieved.

For example, for chronic diseases, the dosing can be adjusted until symptoms are managed, stabilized and/or ameliorated.

The amount of a composition to be administered will, of course, be dependent on the subject being treated, the severity of the affliction, the manner of administration, the immune state of the subject, the judgment of the prescribing physician, etc.

Compositions of some embodiments of the invention may, if desired, be presented in a pack or dispenser device, such as an FDA approved kit, which may contain one or more unit dosage forms containing the active ingredient. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be accommodated by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions or human or veterinary administration. Such notice, for example, may be of labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert. Compositions comprising a preparation of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition, as is further detailed above.

As used herein the term “about” refers to ±10%

The terms “comprises”, “comprising”, “includes”, “including”, “having” and their conjugates mean “including but not limited to”.

The term “consisting of” means “including and limited to”.

The term “consisting essentially of” means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

As used herein, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof. Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging/ranges between” a first indicate number and a second indicate number and “ranging/ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

As used herein, the term “treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

When reference is made to particular sequence listings, such reference is to be understood to also encompass sequences that substantially correspond to its complementary sequence as including minor sequence variations, resulting from, e.g., allelic variation, sequencing errors, cloning errors, or other alterations resulting in base substitution, base deletion or base addition, provided that the frequency of such variations is less than 1 in 50 nucleotides, alternatively, less than 1 in 100 nucleotides, alternatively, less than 1 in 200 nucleotides, alternatively, less than 1 in 500 nucleotides, alternatively, less than 1 in 1000 nucleotides, alternatively, less than 1 in 5,000 nucleotides, alternatively, less than 1 in 10,000 nucleotides.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.

EXAMPLES

Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non limiting fashion.

Generally, the nomenclature used herein and the laboratory procedures utilized in the present invention include molecular, biochemical, microbiological and recombinant DNA techniques. Such techniques are thoroughly explained in the literature. See, for example, “Molecular Cloning: A laboratory Manual” Sambrook et al., (1989); “Current Protocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et al., “Current Protocols in Molecular Biology”, John Wiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide to Molecular Cloning”, John Wiley & Sons, New York (1988); Watson et al., “Recombinant DNA”, Scientific American Books, New York; Birren et al. (eds) “Genome Analysis: A Laboratory Manual Series”, Vols. 1-4, Cold Spring Harbor Laboratory Press, New York (1998); methodologies as set forth in U.S. Pat. Nos. 4,666,828; 4,683,202; 4,801,531; 5,192,659 and 5,272,057; “Cell Biology: A Laboratory Handbook”, Volumes I-III Cellis, J. E., ed. (1994); “Current Protocols in Immunology” Volumes I-III Coligan J. E., ed. (1994); Stites et al. (eds), “Basic and Clinical Immunology” (8th Edition), Appleton & Lange, Norwalk, Conn. (1994); Mishell and Shiigi (eds), “Selected Methods in Cellular Immunology”, W. H. Freeman and Co., New York (1980); available immunoassays are extensively described in the patent and scientific literature, see, for example, U.S. Pat. Nos. 3,791,932; 3,839,153; 3,850,752; 3,850,578; 3,853,987; 3,867,517; 3,879,262; 3,901,654; 3,935,074; 3,984,533; 3,996,345; 4,034,074; 4,098,876; 4,879,219; 5,011,771 and 5,281,521; “Oligonucleotide Synthesis” Gait, M. J., ed. (1984); “Nucleic Acid Hybridization” Hames, B. D., and Higgins S. J., eds. (1985); “Transcription and Translation” Hames, B. D., and Higgins S. J., Eds. (1984); “Animal Cell Culture” Freshney, R. I., ed. (1986); “Immobilized Cells and Enzymes” IRL Press, (1986); “A Practical Guide to Molecular Cloning” Perbal, B., (1984) and “Methods in Enzymology” Vol. 1-317, Academic Press; “PCR Protocols: A Guide To Methods And Applications”, Academic Press, San Diego, Calif. (1990); Marshak et al., “Strategies for Protein Purification and Characterization—A Laboratory Course Manual” CSHL Press (1996); all of which are incorporated by reference as if fully set forth herein. Toxoplasma gondii: the model apicomplexan—Perspectives and methods. L M Weiss, K Kim, 2011. Other general references are provided throughout this document. The procedures therein are believed to be well known in the art and are provided for the convenience of the reader. All the information contained therein is incorporated herein by reference.

General Materials and Experimental Methods

Toxoplasma gondii Culture

Parasites were grown on human foreskin fibroblasts (HFF) in Dulbecco's modified Eagle's medium (DMEM) supplemented with 2 mM L-Glutamine, Penicillin and Streptomycin or Gentamicin antibiotic mix and 10% Fetal Bovine Serum (FBS), thereby referred to as “complete DMEM media”. Cultures were monitored daily, and the parasites were passaged by transferring a drop of the supernatant of a lysed dish or a drop of syringe-released intracellular parasites into a fresh dish with HFF.

Generation of T. gondii Expression Vectors for Expression of Heterologous Polypeptides Comprised of a Toxoplasma Secreted Protein Fused to a Pharmaceutical Polypeptide-of-Interest

In order to generate stable transgenic lines of T. gondii that express specific therapeutic proteins, the present inventors first generated T. gondii expression constructs by molecular cloning. The constructs include a long open reading frame (ORF), which consists of Toxofilin cDNA [SEQ ID NO: 4481] or GRA16 cDNA [SEQ ID NO: 4472] followed by an HA tag coding sequence (SEQ ID NO: 4474) followed by the therapeutic mammalian cDNA of interest, such as the murine MeCP2 isoform 1 [SEQ ID NO: 4476]; the human ASPA [SEQ ID NO: 4483], the human SMN1 [SEQ ID NO: 4479]; the human PARK2 [SEQ ID NO: 4478]; the human GDNF [SEQ ID NO: 4489]; the human TFEB (Transcription factor EB) isoform 1 [SEQ ID NO: 4600] sequence; the human GALC isoform 1 [SEQ ID NO:4486 or SEQ ID NO:4601 (GALC version 2); the GALC-TAT that includes a Glycine flexible linker (Gly) [SEQ ID NO:4490] followed by a protein transduction domain (TAT) that facilitates nonclassical trafficking across membranes in order to aid the targeting of GALC to the lysosome of the host cell (SEQ ID NO: 4488) or the “mutated GALC-TAT” (GALC-TAT that harbors a deletion) (SEQ ID NO: 4487). The cDNA of interest can also be codon-optimized according to the codon usage of T. gondii in order to increase efficiency of expression, stability and localization of the heterologous polypeptide in T. gondii (such as with the codon optimized murine MeCP2 isoform 1 [SEQ ID NO: 4477], codon optimized human ASPA [SEQ ID NO: 4602], codon optimized human GALC isoform 1 [SEQ ID NO: 4603] and codon optimized human TFEB isoform 1 [SEQ ID NO: 4604] codon optimized for expression in T. gondii). The T. gondii expression vector also includes regulatory elements from the same or other Toxoplasma genes that guarantee its correct expression and targeting. Upstream of the ORF is the endogenous 5′ regulatory sequence which can be either the endogenous 5′ regulatory sequence of the Toxofilin gene, here referred to as the “Toxofilin promoter” or “Toxofilin 5′-UTR” (SEQ ID NO: 4482) or the endogenous 5′ regulatory sequence of the GRA16 gene, here referred to as the “GRA16 promoter” or “GRA16 5′-UTR” (SEQ ID NO: 4473). Downstream of the ORF is the 3′-UTR of the abundant dense granule protein GRA2 (SEQ ID NO: 4491; FIG. 3). The expression vector also included a separate ORF containing the selectable markers HXGPRT [SEQ ID NO: 4475] or DHFR-TS [SEQ ID NO: 4484 or 4606] or mCherry [SEQ ID NO: 4608], surrounded by the 5′ UTR of DHFR-TS (upstream) [SEQ ID NO:4492] and 3′ UTR of DHFR-TS (downstream) [SEQ ID NO: 4493 or 4609].

Generation of Transgenic T. gondii

T. gondii of the type I strains RH or RHAHX or the type II strains Prugniaud, Prugniaud-GFP-Luciferase or Prugniaud ΔHPT (also known as Prugniaud ΔHX) were used for generating transgenic strains. Extracellular Tachyzoites were collected or mechanically egressed using a 22-26 gauge needle, filtered from cellular debris, pelleted and resuspended in 300 μl cytomix buffer (120 mM KCl, 0.15 mM CaCl₂ 10 mM K₂HPO₄/KH₂PO₄ pH 7.6, 25 mM HEPES pH 7.6, 2 mM EGTA, 5 mM MgCl₂) with freshly added 2 mM ATP and 5 mM GSH in 30 μl each (360 μl total). 20-60 μg plasmid DNA, or DNA linearized with the enzyme ScaI was transfected into the tachyzoites by electroporation with a BTX ECM electroporator. A few drops of the transfected cells were transferred onto IFA wells (immunofluorescence assay wells of a 24-well plate with HFF cells seeded on glass coverslips) and immunofluorescently stained for assessment of transfection efficiency and transient protein expression (expression from plasmid DNA). The rest of the transfected parasites were transferred onto a fresh flask with HFF in complete DMEM. If a drug-resistance selectable marker was used, the next day media was changed to fresh media containing the drug used for selection (1 μM pyrimethamine for DHFR-TS selection or 25 μg/ml mycophenolic acid+50 μg/ml xanthine for HXGPRT selection). Starting from the day the parasites started egressing from the HFF, drops of the supernatant containing extracellular parasites were passed every 1-2 days into a second flask of HFF in selective media containing the selection drug. When the parasites in the second flask started egressing from the HFF, drops of the supernatant were passed every 1-2 days from the second flask into a third flask, and so on. If a fluorescent protein selectable marker was used, when the parasites in the second flask egressed out of about 50%-90% of the HFF cells, the media with extracellular parasites was collected, filtered from cell debris and sorted using a FACS machine. Parasites emitting fluorescence corresponding to the fluorescent protein used for selection were collected and passed into the next flask of HFF in complete DMEM media. After the 3rd-5th flask started lysing (about 2-5 weeks), the parasites were considered a “stable pool” containing parasites that integrated the DNA construct into their genome. A drop of the stable pool was passed onto IFA (immuno fluorescent assay) wells and immunofluorescently stained to assess percentage of construct-positive parasites in the pool, protein expression and protein localization in the genome-integrated (“stable”) parasites (genomic expression). Clonal lines were established by manual sorting by limiting dilutions or by FACS sorting one parasite per well in 96 well plates. Plates were kept undisturbed for 5-10 days, after which they were screened by eye using a bright field microscope to detect wells with a single plaque which is assumed to originate from a single parasite. Wells with a single plaque were mixed vigorously with a pipette and 50 μl of the mixture was passed to a new dish and to a PCR tube. Lysates were made by pelleting the collected cells in the PCR tubes, resuspending them in 10 μl lysis buffer consisted of 10% proteinase K in TE buffer and incubation in 60° C. for 60 minutes followed by 95° C. for 10 minutes in a thermocycler. One microliter (1 μl) of the lysates were used as template for PCR screening using primers specific for the genetic construct. PCR-positive clones were passed onto IFA wells, fixed, immunofluorescently stained and analysed using a fluorescent microscope and polarized light microscope for protein expression and protein localization in each clone.

Antibodies

Antibodies and the respective concentrations they were used in, are as follows: anti-HA (Roche, IFA: 1:1000, WB: 1:1000), anti-IMC-1 (gift from Prof. Dominique Soldati-Favre, IFA: 1:1000-1:2000), anti-MeCP2 (Cell Signaling, IFA: 1:200, WB: 1:1000, IP: 1:26), anti-NeuN (Abcam, IFA: 1:500), anti-NCoR1 (Bethyl Laboratories, WB: 1:1000), anti-TBL1 (Abcam, WB: 1:1000), Alexa Fluor anti-rat 488 and 594 (Invitrogen, IFA: 1:1000), Alexa Fluor anti-rabbit 488 and 594 (Invitrogen, IFA: 1:1000), Alexa Fluor anti-mouse 488 and 594 (Invitrogen, IFA: 1:1000).

Example 1 Generation of T. gondii Construct which Leads to the Expression, Localization to Parasite's Secretory Organelles and Secretion of a Therapeuic Protein-of-Interest into the Host Cell

Experimental Procedures

The constructs were transfected into RH (RHhxgprt) or Pru (Pruhxgprt) strain T. gondii parasites by electroporation. This is followed by a process of selection for parasites expressing the selection markers (either Pyrimethamine selection for a construct containing DHFR-TS (SEQ ID NO: 4484), which was co-transfected with the construct-of-interest), or using MPA+Xanthine for selection based on expression of HXGPRT (SEQ ID NO:4475), cloning by limiting dilutions or flow cytometry, and PCR-based screening. The positive clones were verified by Western Blot analysis and by immunofluorescence staining to characterize the expression and specific localization of the HA-tagged therapeutic protein in the secretory rhoptry organelles, dense granule organelles, parasitophorous vacuole space, parasitophorous vacuole membrane, or in the host cells. The verified positive lines were further maintained on HFF (human foreskin fibroblast) cells.

Experimental Results

Generation of Constructs and T. gondii Strains for Delivery of the Therapeutic Proteins Galactocerebrosidase, Galactocerebrosidase-TAT, GDNF, Aspartoacylase, MeCP2, Survival Motor Neuron Protein and E3 Ubiquitin Protein Ligase Parkin—

The results demonstrate that T. gondii can be engineered to express heterologous (mammalian, e.g., human) therapeutic proteins fused to an endogenous protein of the parasite. Using this approach, the present inventors have generated 3 novel stable T. gondii transgenic lines expressing the 3 human proteins associated with common neuropathologies, Galactocerebrosidase-TAT (the mutated GALC-TAT SEQ ID NO: 4487), MeCP2 (codon optimized SEQ ID NO: 4477) and GDNF (SEQ ID NO: 4489), and additional 4 mixed-population pools containing stable T. gondii transgenic parasites expressing the 3 human proteins associated with common neuropathologies Galactocerebrosidase (GALC, isoform 1, SEQ ID NO:4486), Galactocerebrosidase-TAT (the WT GALC-TAT SEQ ID NO: 4488), Aspartoacylase (ASPA SEQ ID NO:4483) and Survival Motor Neuron Protein (SMN1, SEQ ID NO: 4479).

Improving Secretion and Uptake of the Therapeutic Protein by a Viral Protein Transduction Domain—

In order to improve secretion of the Galactocerebrosidase protein from the host cell to the extracellular space, as well as the uptake of the protein by neighboring cells, the present inventors have fused Galactocerebrosidase to a viral protein transduction domain (PTD). Tat-PTD has been previously shown to significantly increase (by 6 fold) the cross-correction efficiency of Galactocerebrosidase through enhancing both the secretion and uptake of the enzyme in a cell culture model system (Meng, X.-L., et al., 2013).

Localization of the Therapeutic Proteins Galactocerebrosidase-TAT, Aspartoacylase, MeCP2 and Survival Motor Neuron Protein to T. gondii Rhoptries Secretory Organelles—

The results demonstrate that T. gondii can localize heterologous (mammalian, e.g., human) therapeutic proteins to the parasite's rhoptries secretory organelles (FIG. 4A), from which they could potentially be released into the host cell cytoplasm and localize to target sites within the infected cell. The fusion proteins containing Galactocerebrosidase-TAT, Aspartoacylase, MeCP2 and Survival Motor Neuron Protein localized to the parasite rhoptries as reported for previous Toxofilin fusions that evidently made their way into the host cell. This was proven by immunofluorescence staining (IFAs) (FIGS. 4B-I).

Thus, the present inventors have succeeded in demonstrating that T. gondii may be engineered to express heterologous (mammalian, e.g., human) proteins fused to an endogenous protein of the parasite, and that these proteins localize to the parasite's rhoptries secretory organelles. The present inventors have engineered the human proteins to be fused to Toxofilin, an endogenous protein that is naturally secreted into host cells by the parasites, which allows to “ride” on the parasite's protein secretion machinery for the targeting and secretion of proteins of interest (e.g., a therapeutic protein). This is an important milestone on the path to suggesting T. gondii as a feasible basis for this technology.

Using this approach, the present inventors have generated a novel stable T. gondii transgenic line, expressing and localizing to the rhoptries the human protein associated with Krabbe disease Galactocerebrosidase-TAT (the mutated GALC-TAT SEQ ID NO: 4487), and additional 4 mixed-population pools containing stable T. gondii transgenic parasites expressing and localizing to the rhoptries the 3 human proteins associated with common neuropathologies Galactocerebrosidase-TAT (the WT GALC-TAT SEQ ID NO: 4488), Aspartoacylase (ASPA SEQ ID NO:4483), MeCP2 (SEQ ID NO:4477) and Survival Motor Neuron Protein (SMN1, SEQ ID NO: 4479).

Localization of the Therapeutic Proteins Aspartoacylase, MeCP2 and Survival Motor Neuron Protein to T. gondii Dense Granules Secretory Organelles and Parasitophorous Vacuolar Space—

The results demonstrate that T. gondii can localize the heterologous (mammalian) human therapeutic proteins to the parasite's Dense granules secretory organelles and parasitophorous vacuolar space (FIG. 5A), from which they could be released into the host cell cytoplasm and localize to target sites within the infected cell (FIGS. 5B-I). As this approach of using sequences from dense granule proteins to drive the secretion of a protein of interest from the parasite dense granules is unprecedented, this is the first time mammalian proteins have been found to be secreted into the parasitophorous vacuolar space by fusion to a dense granule protein (GRA16). This was proven by immunofluorescence staining (IFAs) (FIGS. 5B-I). The fusion proteins are then expected to pass through the parasitophorous vacuolar membrane into the host cell, based on the known localization of the native GRA16 protein they are fused to (Bougdour et al. 2013).

Thus, the present inventors have succeeded in demonstrating that T. gondii may be engineered to express heterologous (mammalian) proteins fused to an endogenous protein of the parasite, and that these proteins localize to the parasite's Dense granules secretory organelles and parasitophorous vacuolar space. The present inventors have engineered the human proteins to be fused to GRA16, an endogenous protein that is naturally secreted into host cells by the parasites, which allows to “ride” on the parasite's protein secretion machinery for the targeting and secretion of proteins of interest (e.g., a therapeutic protein). This is an important milestone on the path to suggesting T. gondii as a feasible basis for this technology.

Using this approach, the present inventors have generated a novel stable T. gondii transgenic line, expressing and localizing to the Dense granule secretory organelles and parasitophorous vacuolar space the human protein associated with Rett Syndrome MeCP2, and additional 2 mixed-population pools containing stable T. gondii transgenic parasites expressing and localizing to the Dense granule secretory organelles and parasitophorous vacuolar space the two human proteins associated with common neuropathologies Aspartoacylase and Survival Motor Neuron Protein.

Secretion of the Therapeutic Protein MeCP2 from the Transgenic Parasite into the Host Cell, and Localization in the Region of Activity in the Host Cell, the Nucleus—

The results demonstrate that protein fusions consisting of a pharmaceutical polypeptide fused to a Toxoplasma gondii secreted polypeptide (and specifically here, the therapeutic protein MeCP2 fused to the T. gondii dense granule protein GRA16), can be released from the parasite into the host cell and translocate to the therapeutic protein's target site in the host cell (here, the nucleus). The fusion protein containing MeCP2 localized to the host cell nucleus as shown by immunofluorescence staining (IFAs) (FIGS. 5F-I). This is an important milestone on the path to suggesting T. gondii as a feasible basis for this technology.

Using this approach, the present inventors have generated novel stable T. gondii transgenic lines, expressing and localizing to the host cell nucleus the human protein associated with Rett Syndrome, MeCP2 (FIGS. 5F-I).

Example 2 Rescue of Galactocerebrosidase Deficiency Through Parasitic Delivery

The Galactocerebrosidase enzymatic activity assay which is based on the enzymatic breakup of a synthetic fluorescent substrate of Galactocerebrosidase named 6-Hexadecanoylamino-4-methylumbelliferyl-beta-D-galactoside (6HMU-beta-D-galactoside) is based on the manufacturer's protocol [Otto P. van Diggelen. MOSCERDAM SUBSTRATES, Laboratory protocol for enzyme analysis for Krabbe disease; Galactocerebrosidase]. Using Krabbe patient-derived fibroblasts, the assay is used to evaluate the ability of the GALC- and GALC-TAT-expressing parasite's to rescue Krabbe disease phenotypes in culture. Untreated Krabbe disease cells (Krabbe patient-derived fibroblasts), Krabbe disease cells transfected with sham vector (empty human expression vector) and/or Krabbe disease cells infected with T. gondii parasites not expressing GALC are used as negative controls. Positive controls are wild type (WT) cell lines, or the Krabbe disease cells transfected with human expression vectors driving the expression of either the standalone (HA-tagged) GALC or GALC-TAT gene or a Toxofilin/GRA16-fused GALC or GALC-TAT gene, identical to the fusion expressed by the transgenic parasites tested. This allows ruling out the possibility that any negative results could be caused by a lack of sufficient effect of the protein itself, or from disruption of the therapeutic protein's activity by the fusion of Toxofilin or GRA16 to the N-terminus of the therapeutic protein, and thus allows quantifiable and direct inference of the efficiency of the parasitic delivery system.

The assay is used to characterize the Galactocerebrosidase-expressing parasites' ability to rescue the Galactocerebrosidase-deficiency shown in Krabbe disease patient-derived fibroblasts. This experiment demonstrates the transgenic parasites' ability to rescue Krabbe disease by delivering the supplementary protein to cells in culture.

Example 3 Rescue of MECP2 Deficiency Through Parasitic Delivery

Neural and glial cells derived from mouse models of Rett syndrome that harbor a mutation or deletion of the MECP2 gene present an array of abnormal morphological and molecular characteristics. [Percy, A. Rett syndrome: coming to terms with treatment. Adv. Neurosci. (2014), [de la Torre-Ubieta et al. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016].

Using a Rett Syndrome cell culture model, the quantitative scoring of the molecular and morphological characteristic phenotypes of Rett syndrome is used to evaluate the ability of the MeCP2-expressing parasite's to rescue Rett Syndrome phenotypes in culture. Untreated Rett Syndrome model cells, Rett Syndrome model cells transfected with sham vector and/or Rett Syndrome model cells infected with T. gondii parasites not expressing MeCP2 are used as negative controls. Positive controls are WT cell lines and Rett Syndrome model cells transfected with human expression vectors driving the expression of either the standalone (HA-tagged) MECP2 coding sequence or a Toxofilin/GRA16-fused MECP2 coding sequence identical to the fusion expressed by the transgenic parasites tested. This allows ruling out the possibility that any negative results could be caused by a lack of sufficient effect of the protein itself, or from disruption of the therapeutic protein's activity by the fusion of Toxofilin or GRA16 to the N-terminus of the therapeutic protein, and thus allows quantifiable and direct inference of the efficiency of the parasitic delivery system.

The assay is used to characterize the MeCP2-expressing parasites' ability to rescue the MeCP2-deficiency shown in a Rett Syndrome cell culture model. This experiment demonstrates the transgenic parasites' ability to rescue a Rett Syndrome by delivering the supplementary protein to cells in culture.

Example 4 Testing Therapeutic Potential of the Transgenic Parasite Lines in Animal Models

The transgenic lines of the parasite are tested for their ability to affect phenotypes in whole organism. Testing the transgenic parasites in mice allows the assessment of the system in the presence of an immune system and a functional blood brain barrier (BBB). The transgenic T. gondii parasites are administered to the respective animal model of the condition being tested intranasally, enterally (such as orally), subcutaneously, intra-muscularly, intravenously, intradermally, intraperitoneally, intracranially or intracerebrally. The transgenic T. gondii parasites are administered in the form of tachyzoites, bradyzoite tissue cysts or oocysts.

Following inoculation with the parasites, the animal model are characterized and assessed for the manifestation of phenotypes related to the condition studied (such as pathological phenotypes of the disease). Phenotypes include behavioral, morphological and molecular phenotypes. The effects of the transgenic parasites are revealed by comparison to animals treated with parasites not expressing the therapeutic polypeptide and to sham-treated animals.

For instance, mice model of Rett Syndrome treated with T. gondii parasites expressing the therapeutic protein MeCP2 are assessed by known phenotypes of the disease which include impaired social interaction, increased scent marking, hindlimb clasping, reduced lifspan, anxiety, respiratory problem, hypoactivity, impaired motor coordination, miRNA-mediated IGF1 deficit, decreased level of BDNF, impaired cortical plasticity, glial dysfunction, GABAergic neuronal dysfunction, decreased soma size, decreased dendritic spine density, decreased synapse number, decreased activity (Ca2+ imaging), decreased sEPSC and sIPSC frequency and amplitude, decreased Tujl+ cell number, decreased PAX6, SCN1A/1B expression, decreased dendrite complexity in cortical neurons, decreased AP frequency in cortical neurons, decreased total transcription in cortical neurons, decreased expression of neuronal, synaptic, highly-expressed genes, immediate early genes and mitochondrial genes in cortical neurons, decreased mRNA translation in cortical neurons, decreased BDNF secretion from cortical neurons, decreased AKT/mTOR pathway activity in cortical neurons and decreased oxygen consumption and maximal respiration in cortical neurons [de la Torre-Ubieta et al. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016.]

Example 5 Generation of Constructs and T. gondii Strains for Delivery of Customized Transcription Activator-Like Effectors (Tales)

T. gondii are engineered to express and secrete customized Transcription activator-like effectors (TALE). Customized TALEs can be used for a wide variety of genome engineering applications, including transcriptional modulation and genome editing. The DNA recognition and binding region of TALEs are made up of tandem repeats of 34-aa sequences (monomers) which determine the sequence of the recognized DNA sequence. There are 4 types of monomers which differ in their repeat variable diresidues (RVDs) which determines the nucleotide they recognize. The monomer termed “NI” (SEQ ID NO: 4508) is specific for the “A” nucleotide; the monomer termed “HD” (SEQ ID NO: 4495) is specific to the “C” nucleotide”; the monomer termed “NG” (SEQ ID NO: 4509) is specific to the “T” nucleotide and the monomer termed “NN” (SEQ ID NO: 4494) is specific the “G” or “A” nucleotide. More recently, the additional RVD NH (SEQ ID NO:4504) was shown to provide higher G-specificity. The tandem repeat DNA-binding domain always ends with a half-length repeat (0.5 repeat). Customized TALE DNA-binding domains can be used to generate custom TALE transcription factors (TALE-TFs) and modulate the transcription of endogenous genes from the genome, by fusion to the synthetic VP64 transcriptional activator. Customized TALE DNA-binding domains can also be used to generate custom TALE nucleases (TALENs) and can be used to generate site-specific double-strand breaks to facilitate genome editing through nonhomologous repair or homology directed repair, by fusion to the catalytic domain of FokI endonuclease. The TALEs are made by constructing a DNA-binding domain from the monomers (SEQ IDs NO:4508, 4509, 4494, 4495 and 4504), which is inserted into a TALEN backbone or TALE-TF backbone. Because the backbones also include the 0.5 repeat at the end of the DNA binding domain, there are 4 types of TALEN backbones (e.g., SEQ ID NOs:4500, 4501, 4502, and 4503), as well as 4 TALE-TF backbones (e.g., SEQ ID NO:4496, 4497, 4498, and 4499). The backbones also contain cytomegalovirus promoter (CMV), nonrepetitive N terminus from the Hax3 TALE (N-term), nonrepetitive C terminus from the Hax3 TALE (C-term), type IIs restriction sites used for the insertion of custom TALE DNA-binding domains (such as BsaI), negative selection cassette containing the ccdB negative selection gene and chloramphenicol resistance gene (ccdB+CmR), nuclear localization signal (NLS), and either a catalytic domain from the FokI endonuclease (FokI) or synthetic transcriptional activator derived from VP16 protein of herpes simplex virus (VP64) followed by 2A self-cleavage linker (2A) and enhanced green fluorescent protein (EGFP). All are followed by a polyadenylation signal (polyA signal) (Sanjana et al., A transcription activator-like effector toolbox for genome engineering, 2012). The resulting TALE sequences are inserted downstream of the coding sequence of a T. gondii endogenous secreted polypeptide as described in the GENERAL MATERIALS AND EXPERIMENTAL METHODS hereinabove, and the resulting constructs are transfected into T. gondii to produce transgenic T. gondii strains that express and secreted the TALE.

For example, in order to target the TACGTACG (SEQ ID NO: 4505) sequence in a genome of a subject in need thereof, the TALE nuclease construct or the TALE transcription factor construct can be used. In the open reading frame of these constructs the monomers which are specific for targeting the exemplary “target sequence” (SEQ ID NO: 4505) are arranged one after the other, as shown schematically in FIG. 6A (for TALE Nuclease) and FIG. 6B (for TALE transcription factor). Sequence information of these constructs is available in the sequence listing (SEQ ID NOs: 4506 and 4507).

Example 6 Generation of T. gondii Parasites that Express Mammalian Therapeutic Proteins and Localize them to their Rhoptry Secretory Organelles

In order to generate T. gondii parasites that express mammalian proteins and target them to their rhoptry secretory organelles the present inventors transfected type I RHΔRX tachyzoites or RH (co-transfected with the pDHFR selection plasmid) T. gondii with plasmids containing sequences coding for the protein of interest fused to the rhoptry protein Toxofilin. The mammalian proteins tested in the Toxofilin fusion system were: glial derived neurotrophic factor (GDNF), parkin (PARK2), galactocerebrosidase (GALC), galactocerebrosidase fused to a TAT protein transduction domain (GALC-TAT; SEQ ID NO: 4487), methyl CpG binding protein (MeCP2), aspartoacylase (ASPA) and Survival of motor neuron (SMN1). In an attempt to improve protein expression and targeting, the present inventors also tested codon-optimized versions of some of the proteins, including GALC, MECP2, ASPA and the additional gene TFEB which was tested in the codon-optimized form (SEQ ID NO: 4604).

ASPA (SEQ ID NO: 4483), ASPA codon optimized (SEQ ID NO: 4602), GALC (SEQ ID NOs: 4486 and 4601), GALC-TAT (SEQ ID NO: 4488), PARK2 (SEQ ID NO: 4478), SMN1 (SEQ ID NO: 4479), GDNF (SEQ ID NO:4489), MeCP2 (SEQ ID NO: 4476) and MeCP2 codon optimized (SEQ ID NO:4477) showed variable targeting of the fusion proteins in the parasites, which included rhoptry targeting as well as other patterns of targeting, resembling endoplasmic reticulum, golgi, nucleus, cytoplasm, apicoplast, microneme and other localizations in the parasites (FIGS. 9A-N).

GALC-TAT mutated form generated primarily rhoptry-like fusion protein localization. From GALC-TAT mutated the present inventors also generated clonal lines that strongly expressed the fusion protein and targeted it to a rhoptries (FIG. 9H).

Example 7 Generation of T. gondii Parasites that Express Mammalian Therapeutic Proteins, Localize them to their Dense Granule Secretory Organelles and Secrete them into the Parasitophorous Vacuole

In order to generate T. gondii parasites that express mammalian proteins and target them to their dense granule secretory organelles type I RHAHX T. gondii were transfected with plasmids containing sequences coding for the protein of interest fused to the dense granule protein GRA16. The mammalian proteins-coding genes tested in the GRA16 fusion system were GALC [human forms (SEQ ID NOs: 4486 and 4601) and codon-optimized (SEQ ID NO: 4603), GALC-TAT (human form SEQ ID NO: 4488), MECP2 (codon-optimized, SEQ ID NO:4477), ASPA [human form (SEQ ID NO:4483) and codon-optimized (SEQ ID NO:4602)], SMN1 (human form, SEQ ID NO: 4479) and TFEB (codon-optimized, SEQ ID NO:4604).

GALC, GALC codon optimized and GALC-TAT were expressed in the transfected parasites (FIGS. 10E, 10F and 10H). ASPA, ASPA codon optimized, SMN1, MeCP2 codon optimized and TFEB codon optimized were expressed and secreted by the dense granules to the parasitophorous vacuole (FIGS. 10C, 10G, 10D, 10I, 10J).

Example 8 Delivery of Mammalian Therapeutic Proteins to Human Fibroblasts in Culture Using Transgenic T. gondii

The present inventors have engineered six Type I and Type II Toxoplasma clonal lines which in addition to secreting the fusion protein into the parasitophorous vacuole, were also able to release it from the parasitophorous vacuole and target it to the nucleus of the host cell in amounts detectable by immunofluorescence staining. These clonal lines are: RH GRA16-MECP2 codon optimized (RH GRA16-MECP2opt), RH GRA16-TFEB codon optimized (RH GRA16-TFEBopt), Prugniaud-GFP-Luciferase DHFR-TS GRA16-MECP2 codon optimized (Pru-GFP-LUC GRA16-MECP2opt), Prugniaud-GFP-Luciferase DHFR-TS GRA16-TFEB codon optimized (Pru-GFP-LUC GRA16-TFEBopt), Prugniaud GRA16-MECP2 codon optimized (Pru GRA16-MECP2opt), and Prugniaud GRA16-TFEB codon optimized (Pru GRA16-TFEBopt). In addition to the transgenic lines expressing the fusion proteins, the present inventors also generated 2 control lines expressing the carrier protein GRA16 fused to the HA epitope tag alone: RH GRA16-HA (RH GRA16-HAstop) and Prugniaud GRA16-HA (Pru GRA16-HAstop). As MeCP2 and TFEB are both nuclear proteins, host cell nuclear targeting means they were targeted to their site of activity in the cell. Secretion and host cell nuclear targeting of the proteins in all the lines described above was detected in HFF human fibroblasts by infection of HFF cells in complete DMEM with tachyzoites of the respective line, fixation, immunofluorescence staining and analysis by fluorescence and polarized light microscopy (FIGS. 10B, 10I and 10J).

In order to quantify the efficiency and the dynamics of GRA16-mediated protein delivery in vitro, the present inventors quantified delivery over time and multiplicity of infection (MOI) for tachyzoites of the three type I lines RH GRA16-HAstop, RH GRA16-MECP2opt and RH GRA16-TFEBopt, as summarized in FIGS. 11A-C.

Example 9 Delivery of Mammalian Therapeutic Proteins to Human Neurons in Culture Using Transgenic T. gondii

Immortalized Human Dopaminergic Neuronal Precursor Cells, also known as Lund Human Mesencephalic (LUHMES) cells, were grown in media containing F12 advanced DMEM media supplemented with L-glutamine, N-2 serum-free supplement and βFGF (beta-fibroblast growth factor). The cells were differentiated in culture into morphologically and biochemically mature dopamine-like neurons using F12 advanced DMEM media supplemented with L-glutamine, N-2 serum-free supplement, tetracycline, GDNF and cAMP (Cyclic adenosine monophosphate). On day 6-9 of differentiation (at which point the cells are mature neurons), tachyzoites of the clonal lines RH GRA16-MECP2opt, RH GRA16-TFEBopt and RH GRA16-HAstop were used to infect the neurons. 16-22 hours post infection the neurons were fixed and immunofluorescently stained and analysed by fluorescence and polarized light microscopy. All lines tested presented clear secretion of the fusion proteins, which were targeted to the nuclei of the human neurons (FIGS. 12A-C).

In addition, human neurons were infected with RH GRA16-MECP2opt tachyzoites and collected 24 hours post infection. Infected neurons were washed with PBS, scraped using a sterile cell scraper and pelleted by centrifugation, residual PBS was removed and the pellets were snap-frozen in liquid nitrogen. Nuclear proteins extracted from the infected neurons were immunoprecipitated using magnetic beads bound to an MeCP2 antibody. Immunoprecipitated proteins were immunoblotted with the same MeCP2 antibody following a standard Western blot protocol. The resulting blot presented 2 strong bands, of approximately 75 kDa and approximately 130 kDa. The ˜75 kDa band represents the endogenous untruncated MeCP2 from the human neurons (predicted size: 75 kDa) and the ˜130 kDa band represents the parasite-delivered GRA16-MeCP2 fusion protein (GRA16 predicted size: 55 kDa. Fusion protein predicted size: 75+55=130 kDa) (FIG. 14).

Example 10 Delivery of Mammalian MECP2 to Mouse Primary Cortical and Hippocampal Cultures Using Transgenic T. gondii and Binding of the Delivered MECP2 to Heterochromatic DNA

Neuron-enriched primary cultures from the cortices and hippocampi of P1 (day 1) mice pups were cultured for 5 days and infected with tachyzoites of the transgenic line RH GRA16-MECP2opt. Twelve (12), 24 and 48 hours post infection, the neurons were fixed, immunofluorescently stained and analysed by fluorescence and polarized light microscopy. In all listed time points, the GRA16-MECP2 fusion protein was secreted and targeted to the nuclei of the neurons, and it also appeared in foci corresponding to areas of dense heterochromatic DNA, recognizes by intense DAPI staining (FIGS. 13A-D). This is a classical marker for MeCP2 functionality as it suggests that it successfully binds on the heterochromatin. Notably, in culture systems T. gondii can infect both neurons, glial and other cells. Because the primary cultures were not purely neuronal (according to NeuN staining), the present inventors could see that non neuronal cells (presumably mostly glia) infected with the transgenic T. gondii also received the MeCP2 fusion protein and presented the same characteristic foci pattern.

Example 11 Expression of GRA16 and GRA16-MECP2 Fusion Protein in T. gondii Bradyzoite Cysts

During the normal course of infection, after the initial acute phase in which the parasite replicates and disseminates in the body as tachyzoites, immune pressure causes T. gondii tachyzoites to differentiate into bradyzoites which resides in the long-lasting quiescent cysts in tissues, and mostly in the brain (Carruthers V B, Suzuki Y, 2007. Schizophr Bull. 33(3):745-51. Effects of Toxoplasma gondii infection on the brain). Therefore the present inventors investigated whether the transgenic T. gondii continue to express the GRA16-fused therapeutic proteins after they differentiate into the bradyzoite form. An in vitro differentiation of the transgenic T. gondii into bradyzoites was induced by stress with alkaline media for 3 to 5 days. Alkaline media contained DMEM medium adjusted to pH 8.1 with 10 mM HEPES and 1% fetal bovine serum supplemented with penicillin-streptomycin (Tomita T, Bzik D J, et al. 2013. PLoS Pathog. 9(12):e1003823. The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence). The present inventors tested differentiation of the strains Pru GRA16-HAstop and Pru GRA16-MeCP2. Bradyzoite cysts, identified by DBA (Dolichos Biflorus Agglutinin) staining of the cyst wall, continue to express both the GRA16-HAstop (Data not shown) and GRA16-MeCP2 proteins (FIGS. 15A-C). This finding shows that the transgenic parasites can continue to express GRA16 and the GRA16 fusion proteins after differentiation into the bradyzoite stage, which is important for continuous secretion and protein delivery from cysts in chronic infections.

Example 12 Probing the Molecular Interactions Between the Heterologous Polypeptides Delivered by T. Gondii and Endogenous Proteins in the Recipient Cell

By performing co-immunoprecipitation on cell lysates from infected cultures and from infected animals, the present inventors can decipher molecular interactions between the polypeptides delivered by the transgenic T. gondii and endogenous proteins and nucleic acids.

For example, in mammalian cells MeCP2 binds both DNA and proteins from the SMRT/NCoR and SIN3A co-repressor complexes. Binding to DNA can be probed by immunofluorescent stainings and by chromatin-immunoprecipitation, and binding to other proteins can be probed by immunofluorescent stainings and by protein co-immunoprecipitation. The added epitope tags on the delivered fusion proteins can be used to distinguish between copies of the protein produced by the host cell and copies of the protein delivered by the parasites, while antibodies against the protein itself can be used to probe both the endogenous and the parasite-delivered protein (e.g. for comparative assays).

Example 13 Testing the Ability of Transgenic T. gondii to Deliver Heterologous Proteins-of-Interest Continuously (/Chronically) in Animal Models

The transgenic lines of the parasite are tested for their ability to affect phenotypes in whole organism. Testing the transgenic parasites in animal models allows the assessment of the system in the presence of an immune system and a functional blood brain barrier (BBB). This is done by following the standard infection protocols established in the field to infect mice with the transgenic T. gondii (Cabral C M et al., 2016, PLoS Pathog. 12(2):e1005447. Neurons are the Primary Target Cell for the Brain-Tropic Intracellular Parasite Toxoplasma gondii; Berenreiterová M et al., 2011. PLoS One. 6(12):e28925. The distribution of Toxoplasma gondii cysts in the brain of a mouse with latent toxoplasmosis: implications for the behavioral manipulation hypothesis; Tait E D et al. 2010. J. Immunol. 185(3):1502-12. Virulence of Toxoplasma gondii is associated with distinct dendritic cell responses and reduced numbers of activated CD8+ T cells; Koshy A A et al. 2012. PLoS Pathog. 8(7):e1002825. Toxoplasma co-opts host cells it does not invade; Jensen K D et al. 2015. MBio. 6(2):e02280. Toxoplasma gondii superinfection and virulence during secondary infection correlate with the exact ROP5/ROP18 allelic combination). The transgenic T. gondii parasites are administered to the animal model intranasally, enterally (such as orally), subcutaneously, intra-muscularly, intravenously, intradermally, intraperitoneally, intracranially or intracerebrally. The transgenic T. gondii parasites are administered in the form of tachyzoites, bradyzoite tissue cysts or oocysts. Animal models can be wild type animals or model animals bearing a condition treatable or otherwise affected by delivery of the protein of interest expressed in the transgenic parasites. After the initial stage of acute infection, the animal develops chronic bradyzoite tissue cysts, primarily in the brain. This mode of delivery relies on continuous expression and secretion the protein of interest from the transgenic T. gondii at the chronic stage of infection.

At different stages during development of the chronic infection (first 3 weeks to 2 months after infection, depending on strain and route of infection), as well as in different time points after the chronic infection has been established and stabilized (time-scale of months to years after infection), brain histological stainings are used to assess the percentage of cells infected, distribution of parasites and the delivered protein in the brain and in other tissues and to quantify the levels of delivered protein. Co-immunoprecipitation and cellular morphologies can be used to confirm molecular interactions between the delivered proteins and endogenous counterparts in the receiving cells and to provide evidence for their function.

The condition of the treated animal model is monitored and characterized at different stages of the chronic infection and at different stages of the disease progression using physiological, behavioural, cellular and molecular measures in order to assess manifestations of disease phenotypes and efficacy of the treatment in alleviating them as well as any potential toxicity arising from the treatment. The effects of the transgenic parasites are assessed by comparison to animals treated with parasites not expressing the pharmaceutical polypeptide and/or to sham-treated animals.

For instance, mice model of Rett Syndrome treated with T. gondii parasites expressing the therapeutic protein MeCP2 are assessed by known phenotypes of the disease which include impaired social interaction, increased scent marking, hindlimb clasping, reduced lifspan, anxiety, respiratory problem, hypoactivity, impaired motor coordination, miRNA-mediated IGF1 deficit, decreased level of BDNF, impaired cortical plasticity, glial dysfunction, GABAergic neuronal dysfunction, decreased soma size, decreased dendritic spine density, decreased synapse number, decreased activity (Ca2+ imaging), decreased sEPSC and sIPSC frequency and amplitude, decreased Tujl+ cell number, decreased PAX6, SCN1A/1B expression, decreased dendrite complexity in cortical neurons, decreased AP frequency in cortical neurons, decreased total transcription in cortical neurons, decreased expression of neuronal, synaptic, highly-expressed genes, immediate early genes and mitochondrial genes in cortical neurons, decreased mRNA translation in cortical neurons, decreased BDNF secretion from cortical neurons, decreased AKT/mTOR pathway activity in cortical neurons and decreased oxygen consumption and maximal respiration in cortical neurons (de la Torre-Ubieta et al. Advancing the understanding of autism disease mechanisms through genetics. Nat Med. 2016, 22:345-61).

Example 14 Testing the Ability of Transgenic T. gondii to Deliver Heterologous Proteins-of-Interest Transiently (/Acutely) in Animal Models

Similarly to Example 13 hereinabove, the transgenic lines of the parasite are tested for their ability to affect phenotypes in whole organism. Testing the transgenic parasites in animal models allows the assessment of the system in the presence of an immune system and a functional blood brain barrier (BBB), and can be conducted by intranasal, enteral (such as oral), subcutaneous, intra-muscular, intravenous, intradermal, intraperitoneal, intracranial or intracerebral administration of the transgenic T. gondii in the form of tachyzoites, bradyzoite tissue cysts or oocysts. Animal models can be wild type animals or model animals bearing a condition treatable or otherwise affected by delivery of the protein of interest expressed in the transgenic parasites. This experimental design focuses on assessment of transient delivery that does not rely on differentiation into bradyzoites and establishment of chronic infection and/or chronic cysts. Some examples include: delivery by attenuated parasites that cannot differentiate into bradyzoites and/or cannot replicate and/or cannot persist in vivo longer than a few weeks, or otherwise cannot establish a chronic infection; delivery by local administration to the target tissue or to an area close to the target tissues followed by clearance or inactivation of the parasites. These can also be repeated multiple times for repeated dosing. Immunosupressive agents can be administered before, concomitantly or after infection with the parasites to enhance infection and to aid re-infection of animals that have already been infected with T. gondii before. This experimental design also includes delivery by transgenic T. gondii capable of establishing chronic infection, but in which the collection of samples or analysis are performed at the acute stage of infection before establishment of chronic infection. This form of delivery relies mostly on secretion of the protein of interest by tachyzoites of the transgenic lines. At different stages during the acute infection (first days to about 2 months after infection, depending on strain and route of infection) brain histological stainings are used to assess the percentage of cells infected, characterize the distribution of parasites and the delivered protein in the brain and in other tissues and quantify the levels of delivered protein. Co-immunoprecipitation and cellular morphologies are used to confirm molecular interactions between the delivered proteins and endogenous counterparts in the receiving cells and to provide evidence for their function.

The condition of the treated animal model is monitored and characterized at different time points after initiation of treatment and at different stages of the disease progression using physiological, behavioural, cellular and molecular measures in order to assess manifestations of disease phenotypes and efficacy of the treatment in alleviating them as well as any potential toxicity arising from the treatment. The effects of the transgenic parasites are assessed by comparison to animals treated with parasites not expressing the therapeutic polypeptide and/or to sham-treated animals.

Example 15 Introduction of Further Modifications that Will Increase the Safety and Controllability of the Transgenic T. Gondii

Although the parasite is generally considered harmless in healthy humans, additional modifications to the parasites may be incorporated in the therapeutic strains in order to further attenuate their virulence. As the model organism of its phylum, there is a wide range of highly developed genetic tools for modifying the parasite (Jiménez-Ruiz E, Wong E H, Pall G S, Meissner M. Parasitology. 2014, 141:1390-8. “Advantages and disadvantages of conditional systems for characterization of essential genes in Toxoplasma gondii”) which may be used to generate attenuated and exogenously-controllable parasites (Moe-Behrens G H, Davis R, Haynes K A. Front Microbiol. 2013 4:5. “Preparing synthetic biology for the world”). One approach may include engineered auxotrophy. Secondly, attenuated parasites may be developed by targeting and disrupting specific virulence mechanisms of the parasite which are not essential to its ability to deliver the protein drugs. Another approach may include active control through engineered induced lethality such as inducible “suicide switches” (self-destruction element) that eliminate the parasite upon administration of an activating molecule. Some examples may include utilizing the widely-used tetracyclin-inducible promoter for drug-inducible activation of lethal or apoptotic pathways in the parasites in vivo, or the rapamycin-dimerizing diCre system for inducible knock-out of essential genes or for inducible activation of lethal or apoptotic pathways. Such drug-inducible control may also allow differential clearance of the parasite from specific tissues, regions or cell types due to differential permeability of the tissues or cells to the drug and its different distribution in the body.

Analysis and Discussion

The invention is a protein delivery platform that utilizes the machinery of the brain parasite T. gondii, which allows it to penetrate the blood-brain barrier and delivery proteins to cells, and especially neurons, within the CNS.

To enable delivery of therapeutic proteins to the CNS, the present inventors reappropriate the parasite Toxoplasma gondii for the synthesis and delivery of proteins of interest to cells in the CNS. The present inventors thus establish a versatile platform for specific and controlled delivery of proteins to cells within the CNS. The engineered parasite has the following novel capabilities:

(1) It can be easily modified to synthesize a range of therapeutic heterologous proteins and secrete them with specificity into target cells within the CNS.

(2) It can contain modification that reduce or exclude elements of the parasite that can mediate deleterious effects on the infected host.

(3) It can contain regulatory and/or self-destruction elements that allow control of its distribution and spatiotemporal activity once in the host.

Following is a non-limiting summary of alterations in the parasite's genome that are described herein:

(i) Fusion of the selected therapeutic protein to a specific endogenous secreted protein of the parasite. Additional accessory elements and modifications may be added to the fusion gene/protein that may increase the effectiveness of the therapeutic fusion protein, such as cleavage sites that may allow detachment of the therapeutic protein from the endogenous parasite protein, after it is no longer needed for its targeting or activity, or mediate detection and assessment of efficiency and distribution of the Toxoplasma and of the delivered protein, such as epitope tags and fluorescent proteins.

(ii) Removal of virulence genes that are not necessary for the therapeutic role of the parasite. These modifications reduce the potential deleterious effects of the parasite on the patient, and makes it relevant for safe clinical use.

(iii) Insertion of regulatory elements that can be induced to cause the parasite to self-destruct in response to an externally administered drug, or to manipulate the parasite's activity. These elements augment the safety features of the technology, and also provide increased control of its spatiotemporal activity.

The initial strains which were developed with the method of some embodiments of the invention were based on the Galactocerebrosidase and Galactocerebrosidase-TAT proteins for Krabbe disease, GDNF protein for a range of neurodegenerative diseases and other conditions (among them Parkinson's disease, Supranuclear Palsy, Multiple sclerosis, Alzheimers disease, Amyotrophic Lateral Sclerosis, Huntington's disease, retinal degenerations, Traumatic Brain Injury and hypoxic/ischaemic CNS disorders), Aspartoacylase protein for Canavan disease, MeCP2 protein for Rett Syndrome, SMN protein for Spinal Mascular Atrophy, E3 ubiquitin-protein ligase parkin for Parkinson's Disease and TFEB for lysosomal storage diseases and neurodegenerative diseases. Though the present inventors have selected a number of therapeutic proteins that are currently being tested clinically and have known supplementary functions, the platform may be adapted to a wide range of proteins.

The possible applications of the technology include, but are not limited to:

1. The treatment of conditions through the delivery of therapeutic proteins;

2. The supply of proteins to the brain in healthy individuals for the purpose of augmenting brain functions or promoting neuro-regeneration;

3. A general solution for highly specific and efficient targeted protein delivery for supplementing protein synthesis.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

REFERENCES

-   1. Pardridge, W. M. Targeted delivery of protein and gene medicines     through the blood-brain barrier. Clin. Pharmacol. Ther. 97, 347-61     (2015). -   2. Cox, D. B. T., Platt, R. J. & Zhang, F. Therapeutic genome     editing: prospects and challenges. Nat. Med. 21, 121-131 (2015). -   3. Persons, D. A. & Baum, C. Solving the problem of γ-retroviral     vectors containing long terminal repeats. Mol. Ther. 19, 229-31     (2011). -   4. Schambach, A., Zychlinski, D., Ehrnstroem, B. & Baum, C.     Biosafety features of lentiviral vectors. Hum. Gene Ther. 24, 132-42     (2013). -   5. Gray, S. J., Nagabhushan Kalburgi, S., McCown, T. J. & Jude     Samulski, R. Global CNS gene delivery and evasion of     anti-AAV-neutralizing antibodies by intrathecal AAV administration     in non-human primates. Gene Ther. 20, 450-9 (2013). -   6. Templeton, N. Gene and cell therapy: therapeutic mechanisms and     strategies. (2008). -   7. Dimmeler, S., Ding, S., Rando, T. A. & Trounson, A. Translational     strategies and challenges in regenerative medicine. Nat. Med. 20,     814-21 (2014). -   8. Abbott, N.J. Blood-brain barrier structure and function and the     challenges for CNS drug delivery. J. Inherit. Metab. Dis. 36, 437-49     (2013). -   9. Malhotra, M. & Prakash, S. Targeted Drug Delivery Across     Blood-Brain-Barrier Using Cell Penetrating Peptides Tagged     Nanoparticles. Curr. Nanosci. 7, 81-93 (2011). -   10. Bradbury, M. W. B. Physiology and Pharmacology of the     Blood-Brain Barrier. (Springer Science & Business Media, 2012). -   11. Solaro, R., Chiellini, F. & Battisti, A. Targeted Delivery of     Protein Drugs by Nanocarriers. Materials (Basel). 3, 1928-1980     (2010). -   12. Sanecka, A. & Frickel, E.-M. Use and abuse of dendritic cells by     Toxoplasma gondii. Virulence 3, 678-89 (2012). -   13. Carruthers, V. B. & Suzuki, Y. Effects of Toxoplasma gondii     infection on the brain. Schizophr. Bull. 33, 745-51 (2007). -   14. Feustel, S. M., Meissner, M. & Liesenfeld, O. Toxoplasma gondii     and the blood-brain barrier. Virulence 3, 182-92 -   15. Montoya, J. G. & Liesenfeld, O. Toxoplasmosis. Lancet 363,     1965-76 (2004). -   16. Dlugonska, H. Toxoplasma rhoptries: unique secretory organelles     and source of promising vaccine proteins for immunoprevention of     toxoplasmosis. J. Biomed. Biotechnol. 2008, 632424 (2008). -   17. Carruthers, V. B. & Sibley, L. D. Sequential protein secretion     from three distinct organelles of Toxoplasma gondii accompanies     invasion of human fibroblasts. Eur. J. Cell Biol. 73, 114-23 (1997). -   18. Boothroyd, J. C. & Dubremetz, J.-F. Kiss and spit: the dual     roles of Toxoplasma rhoptries. Nat. Rev. Microbiol. 6, 79-88 (2008). -   19. Koshy, A. A. et al. Toxoplasma secreting Cre recombinase for     analysis of host-parasite interactions. Nat. Methods 7, 307-9     (2010). -   20. Fox, B. A., Sanders, K. L. & Bzik, D. J. Non-replicating     Toxoplasma gondii reverses tumor-associated immunosuppression.     Oncoimmunology 2, e26296 (2013). -   21. Fox, B. A., Sanders, K. L., Chen, S. & Bzik, D. J. Targeting     tumors with nonreplicating Toxoplasma gondii uracil auxotroph     vaccines. Trends Parasitol. 29, 431-7 (2013). -   22. Elliott, D. E. & Weinstock, J. V. Helminth-host immunological     interactions: prevention and control of immune-mediated diseases.     Ann. N. E Acad. Sci. 1247, 83-96 (2012). -   23. Rothman, J. & Paterson, Y. Live-attenuated Listeria-based     immunotherapy. Expert Rev. Vaccines 12, 493-504 (2013). -   24. Reeves, A. Z. et al. Engineering Escherichia coli into a protein     delivery system for mammalian cells. ACS Synth. Biol. 4, 644-54     (2015). -   25. Meng, X.-L., Eto, Y., Schiffmann, R. & Shen, J.-S. HIV Tat     Domain Improves Cross-correction of Human Galactocerebrosidase in a     Gene- and Flanking Sequence-dependent Manner. Mol. Ther. Nucleic     Acids 2, e130 (2013). -   26. Otto P. van Diggelen. MOSCERDAM SUBSTRATES, Laboratory protocol     for enzyme analysis fir Krabbe disease; Galactocerebrosidase.     MOSCERDAM SUBSTRATES, Laboratory protocol for enzyme analysis fir     Krabbe disease; Galactocerebrosidase. 

What is claimed is:
 1. A method of administering a protein-of-interest into a central nervous system of a subject, the method comprising: administering to the subject a Toxoplasma transformed with a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that said promoter is not a Toxofilin promoter, wherein said toxoplasma secreted protein is secreted to a host cell, and wherein said toxoplasma secreted protein is selected from the group consisting of a rhoptry secreted protein, a microneme protein, a dense granule protein and a Toxoplasma gondii macrophage migration inhibitory factor (TgMIF), and wherein said dense granule protein is selected from the group consisting of GRA16 and GRA24, thereby administering the protein-of-interest to the central nervous system of the subject.
 2. A method of treating a subject in need thereof, comprising administering to the subject a Toxoplasma transformed with a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that said promoter is not a Toxofilin promoter, wherein said toxoplasma secreted protein is secreted to a host cell, wherein said toxoplasma secreted protein is selected from the group consisting of a rhoptry secreted protein, a microneme protein, a dense granule protein and a Toxoplasma gondii macrophage migration inhibitory factor (TgMIF), and wherein said dense granule protein is selected from the group consisting of GRA16 and GRA24, wherein the toxoplasma being devoid of virulence genes which are not necessary for delivery of the protein-of-interest into a central nervous system (CNS) of a subject, and wherein said subject is diagnosed with a pathology treatable by administration of said pharmaceutical polypeptide in a central nervous system of the subject, thereby treating the subject in need thereof.
 3. A method of treating a subject in need thereof, comprising administering to the subject a Toxoplasma comprising a nucleic acid construct which comprises a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said toxoplasma secreted protein is selected from the group consisting of a rhoptry secreted protein, a microneme protein, a dense granule protein and a Toxoplasma gondii macrophage migration inhibitory factor (TgMIF), and wherein said dense granule protein is selected from the group consisting of GRA16 and GRA24, and wherein said subject is diagnosed with a pathology treatable by administration of said pharmaceutical polypeptide in a central nervous system of the subject, thereby treating the subject in need thereof.
 4. A method of administering a polypeptide-of-interest to a subject, comprising administering to the subject a Toxoplasma comprising a nucleic acid construct which comprises a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding the polypeptide-of-interest, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that said promoter is not a toxofilin promoter, and wherein said toxoplasma secreted protein is selected from the group consisting of a rhoptry secreted protein, a microneme protein, a dense granule protein and a Toxoplasma gondii macrophage migration inhibitory factor (TgMIF), and wherein said dense granule protein is selected from the group consisting of GRA16 and GRA24, thereby administering the polypeptide-of-interest to the subject.
 5. The method of claim 1, further comprising administering to the subject an immunosuppression drug prior to administration of said Toxoplasma and/or subsequent to administration of said Toxoplasma and/or concomitantly with administration of said Toxoplasma to the subject.
 6. The method of claim 1, wherein said pharmaceutical polypeptide comprises a wild type amino acid sequence corresponding to said endogenous protein capable of treating the pathology.
 7. The method of claim 1, wherein said pharmaceutical polypeptide comprises an antibody capable of treating the pathology.
 8. The method of claim 1, wherein said pharmaceutical polypeptide comprises a toxin capable of treating the pathology.
 9. The method of claim 1, further comprising administering to the subject a drug capable of inducing a self-destruction element.
 10. The method of claim 1, wherein said toxoplasma persists in said infect host cell.
 11. The method of claim 1, wherein said Toxoplasma secreted protein is secreted continuously.
 12. The method of claim 1, wherein said pharmaceutical polypeptide reaches a nucleus of a host cell.
 13. The method of claim 1, wherein said Toxoplasma secreted protein is selected from the group consisting of a microneme protein and a dense granule protein.
 14. A method of administering a protein-of-interest into a central nervous system of a subject, the method comprising: administering to the subject a Toxoplasma transformed with a nucleic acid construct comprising a heterologous polynucleotide comprising a first nucleic acid sequence encoding a Toxoplasma secreted protein in frame fused upstream to a second nucleic acid sequence encoding a pharmaceutical polypeptide, wherein said heterologous polynucleotide is operably linked to a promoter for directing transcription of said heterologous polynucleotide in a Toxoplasma, wherein said promoter is selected from the group consisting of: a constitutive promoter, an inducible promoter, a latent period-specific promoter, and a Toxoplasma endogenous promoter with the proviso that said promoter is not a Toxofilin promoter, wherein said toxoplasma secreted protein is secreted to a host cell, wherein said Toxoplasma secreted protein is secreted from a dense granule of said Toxoplasma and is selected from the group consisting of GRA16 and GRA24, thereby administering the protein-of-interest to the central nervous system of the subject.
 15. The method of claim 1, with the proviso that said nucleic acid construct does not comprise a Cre-recombinase coding sequence.
 16. The method of claim 1, further comprises at least one in frame cleavage site which allows detachment of said pharmaceutical polypeptide from said Toxoplasma secreted protein.
 17. The method of claim 1, wherein said Toxoplasma is comprised in a pharmaceutical composition which further comprises a pharmaceutically acceptable carrier.
 18. The method of claim 2, wherein said pathology is characterized by a deficient endogenous protein in a central nervous system of a subject. 